ANNUAL REVIEWS

Further

Click here for quick links to Annual Reviews content online, including: • Other articles in this volume • Top cited articles • Top downloaded articles • Our comprehensive search

Physiology and Pharmacology of Striatal Neurons
Anatol C. Kreitzer
Gladstone Institute of Neurological Disease and Departments of Physiology and Neurology, University of California, San Francisco, California 94158; email: akreitzer@gladstone.ucsf.edu

Annu. Rev. Neurosci. 2009.32:127-147. Downloaded from www.annualreviews.org by University of Manchester - John Rylands Library on 10/28/11. For personal use only.

Annu. Rev. Neurosci. 2009. 32:127–47 First published online as a Review in Advance on March 20, 2009 The Annual Review of Neuroscience is online at neuro.annualreviews.org This article’s doi: 10.1146/annurev.neuro.051508.135422 Copyright c 2009 by Annual Reviews. All rights reserved 0147-006X/09/0721-0127$20.00

Key Words
basal ganglia, medium spiny neuron, interneuron, dopamine, acetylcholine

Abstract
The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function.

127

Contents
INTRODUCTION . . . . . . . . . . . . . . . . . . STRIATAL ANATOMY . . . . . . . . . . . . . . Compartments . . . . . . . . . . . . . . . . . . . . . Regions . . . . . . . . . . . . . . . . . . . . . . . . . . . STRIATAL NEUROMODULATORS . . . . . . . . . Dopamine . . . . . . . . . . . . . . . . . . . . . . . . . Acetylcholine . . . . . . . . . . . . . . . . . . . . . . MEDIUM SPINY NEURONS . . . . . . . Membrane Properties . . . . . . . . . . . . . . Up and Down States . . . . . . . . . . . . . . . Neuromodulation . . . . . . . . . . . . . . . . . . INTERNEURONS . . . . . . . . . . . . . . . . . . Fast Spiking Interneurons . . . . . . . . . . Low-Threshold Spiking Interneurons. . . . . . . . . . . . . . . . . . . . Cholinergic Interneurons . . . . . . . . . . CONCLUSIONS . . . . . . . . . . . . . . . . . . . . 128 130 130 130 131 131 132 132 132 134 134 135 135 136 137 138

INTRODUCTION
The striatum is a convergence point for glutamatergic inputs from cortex and thalamus, as well as dopaminergic afferents from the midbrain (Bolam et al. 2000, Kincaid et al. 1998, Smith et al. 1994). It is also the source of the direct and indirect pathways, two parallel basal ganglia circuits that are critical for motor function and procedural learning (Albin et al. 1989, DeLong 1990, Smith et al. 1998). The importance of the striatum for basal ganglia function is highlighted by neurological disorders in which striatal function is compromised (Graybiel 2000). In Parkinson’s disease, dopaminergic afferents to the striatum are lost and striatal output via the direct and indirect pathways is altered, resulting in impaired movement capabilities. In Huntington disease, striatal projection neurons become dysfunctional and degenerate, leading to a disconnection of the striatum from downstream basal ganglia nuclei and severe motor deficits (Albin et al. 1989, DeLong 1990). Striatal dysfunction is also implicated in other
Kreitzer

MSN: medium spiny neuron SNr: substantia nigra pars reticulata GP: globus pallidus DA: dopamine ACh: acetylcholine

neurological disorders including dystonia, obsessive-compulsive disorder, and addiction (Breakefield et al. 2008, Graybiel 2008, Hyman et al. 2006). Thus, understanding striatal physiology is of paramount importance to deciphering basal ganglia function in health and disease. Striatal neurons (Figure 1a–d ) have been characterized at the anatomical, histochemical, and physiological levels (Kawaguchi et al. 1995, Wilson 1993). Anatomically, striatal cells fall into two main classes: (a) spiny projection neurons and (b) aspiny interneurons. Spiny projection neurons, also known as medium spiny neurons (MSNs), represent the vast majority of striatal neurons. They are GABAergic and can be classified into striatonigral (direct-pathway) and striatopallidal (indirect-pathway) subtypes on the basis of their axonal projections to the substantia nigra pars reticulata (SNr) or the globus pallidus (GP in rodents, external GP in primates) (Smith et al. 1998). MSNs receive glutamatergic inputs from cortex and thalamus that terminate predominantly on spines (Kemp & Powell 1971b). In addition, they are a main target of midbrain dopaminergic neuron axons that form synapses on MSN dendrites and spine necks (Smith et al. 1994). Histochemically, striatonigral MSNs express high levels of D1 and muscarinic M4 receptors, as well as dynorphin and substance P (Gerfen 1992, Ince et al. 1997). In contrast, striatopallidal MSNs are characterized by their high expression of dopamine D2 and adenosine A2A receptors, as well as their immunoreactivity for enkephalin (Gerfen 1992, Schiffmann et al. 1991). Physiologically, striatonigral and striatopallidal MSNs exhibit similar properties, although striatopallidal MSNs exhibit increased excitability (Kreitzer & Malenka 2007) and each type of MSN is differentially modulated by dopamine (DA) and acetylcholine (ACh) (Shen et al. 2007, Surmeier et al. 2007). Aspiny interneurons are far fewer in number and can be categorized anatomically into medium-sized GABAergic cells and large cholinergic cells (Kawaguchi et al. 1995). Medium-sized GABAergic interneurons can

Annu. Rev. Neurosci. 2009.32:127-147. Downloaded from www.annualreviews.org by University of Manchester - John Rylands Library on 10/28/11. For personal use only.

128

(e) A coronal schematic of the mouse forebrain depicting the cortex and striatum.annualreviews.org • Striatal Physiology and Pharmacology FS: fast spiking LTS: low-threshold spiking Bacterial artificial chromosome (BAC) transgenic mice: genetically engineered mice containing a gene of interest and surrounding genomic regulatory elements required for that gene’s cell-type specific expression pattern 129 . However. striatal interneurons are straightforward to identify electrophysiologically (Kawaguchi et al. and the dorsolateral. Finally. Vincent et al. these three classes of GABAergic interneurons display at least two different types of firing patterns (Kawaguchi et al. They also appear similar to MSNs under the light microscope. making them difficult to selectively target for recording. Rev. striatal interneurons receive glutamatergic afferents from cortex and thalamus. and ventral divisions of the striatum are schematically illustrated in the left hemisphere. detailed characterization of these neurons has proven difficult for several reasons. 2003). In the case of MSNs. 1995) but represent only a small fraction of total neuron number. (c) a low-threshold spiking interneuron (LTS). 1983). Drawings based on images from Kawaguchi (1993). Fortunately. it has been impossible to differentiate striatonigral and striatopallidal MSNs in vitro without post hoc analysis because of their similar anatomical and electrophysiological properties. they may also exhibit some characteristics of LTS interneurons (Tepper & Bolam 2004). Physiologically. forming microcircuits capable of modulating striatal output (Tepper et al. 1990). Although calretinin-positive interneurons have not been classified physiologically. 2004). (b) a fast spiking interneuron (FS). 1995. For personal use only. researchers have developed new technologies that enable the visualization of distinct striatal cell types for cellular and synaptic electrophysiology (Gong et al. Bacterial artifical chromosome (BAC) transgenic mice expressing green fluorescent protein in striatonigral or striatopallidal www. Somatostatinpositive interneurons have lower firing rates and plateau potentials and are known as low-threshold spiking (LTS) interneurons. Although investigators have known the basic physiological properties of striatal cell types for some time. Parvalbumin-positive neurons exhibit rapid and sustained firing rates in response to current injection and are alternatively known as fast spiking (FS) interneurons. be further classified histochemically into three subtypes: (a) parvalbumin-positive. (b) somatostatin-.a b MSN FS c Annu. and nitric oxide synthase-positive.org by University of Manchester . Schematic representations of (a) a striatal medium spiny neuron (MSN). 2009. Cowan et al. Like MSNs. and (d ) a cholinergic tonically active neuron (TAN). their output is directed primarily to MSNs and other interneurons. neuropeptide Y-. Tepper & Bolam 2004).John Rylands Library on 10/28/11. Chesselet & Graybiel 1986. 1990. Striatal patches ( pink) are illustrated in the right hemisphere. Neurosci. In contrast. and (c) calretinin-positive (Bennett & Bolam 1993. d LTS TAN Cortex 20 μm e Striatum Figure 1 Cell types and functional organization of the rodent striatum. dorsomedial. cholinergic interneurons can be physiologically characterized by their significant hyperpolarization-activated currents and spontaneous activity under physiological conditions (Wilson et al.annualreviews.32:127-147. Smith & Parent 1986. Downloaded from www.

1988). 2006. the dorsal striatum is divided by the internal capsule into the medially located caudate nucleus and the laterally positioned putamen. as are mouse lines labeling FS and LTS interneurons. the striatum exhibits a relatively uniform appearance. The ventral striatum—or nucleus accumbens—represents a third subdivision of the striatum. However. Ragsdale & Graybiel 1988). McGeorge & Faull 1989). suggesting a possible independent regulation of striatal output by DA in these compartments. Both striatopallidal and striatonigral MSNs are contained in the patch and matrix compartments (Gerfen & Young 1988). like the patches of the dorsal . Patches appear to receive innervation from a distinct set of ventral tier SNc neurons ( Jimenez-Castellanos & Graybiel 1987. making their connectivity similar to MSNs in ventral striatum (Gerfen 1985). This review focuses on the cellular physiology of different striatal neuron types. yielding no clear division between dorsomedial and dorsolateral striatum. whereas the axons of FS interneurons routinely cross compartment boundaries (Cowan et al. Fujiyama et al. Liles & Updyke 1985. Downloaded from www. These new tools have led to a resurgence in striatal research. 1986). Graybiel et al. Matrix MSNs receive inputs from cortex and thalamus (Donoghue & Herkenham 1986. and poor staining for cholinergic markers (Graybiel & Ragsdale 1978). including their membrane properties.32:127-147. whereas other markers label the matrix of neuropil surrounding these patches (Graybiel & Ragsdale 1978. firing patterns. also known as striosomes. The matrix compartment receives the bulk of sensorimotor striatal afferents and appears to be strongly regulated by both DA and ACh. The dense somatostatin and ChAT immunoreactivity in the matrix indicate that the axons of LTS and cholinergic interneurons may be preferentially localized to the matrix (Chesselet & Graybiel 1986. represent ∼10% of striatal volume and are distinguished by dense μ-opioid receptor binding (Herkenham & Pert 1981). Neurosci. Kincaid & Wilson 1996. 1992) and connect to both the SNr and the GP (Gerfen 1992). This patch/matrix organization (Figure 1e) is particularly important during development and segregates MSNs on the basis of their afferent and efferent projections (Gerfen 1992). 2009. However. 1972). although striatonigral MSNs in the patch compartment project to the substantia nigra pars compacta (SNc) rather than to the SNr (Gerfen 1984). Graybiel & Ragsdale 1978). Regions In primates.John Rylands Library on 10/28/11. Ragsdale & Graybiel 1981) and the dorsolateral striatum receives inputs from sensorimotor cortex (Kunzle 1975. Patches. the dorsomedial striatum receives inputs primarily from association cortices (Goldman & Nauta 1977. In rodents. Yin & Knowlton 2006).SNc: Substantia Nigra pars compacta ChAT: choline acetyltransferase MSNs are now readily available. it has long been noted that certain neurochemical markers label patches of striatum. Patch MSNs receive input primarily from limbic and frontal regions (Donoghue & Herkenham 1986.annualreviews. the matrix is defined by rich acetylcholinesterase and choline acetyltransferase (ChAT) staining (Graybiel et al. Olson et al. Prensa & Parent 2001). and modulation by DA and ACh. Parent & Hazrati 1995. substance P staining (Bolam et al. For personal use only. 1986. Rev. STRIATAL ANATOMY Annu. the two most prominent striatal neuromodulators. In contrast. McGeorge & Faull 1989. as well as immunoreactivity for calbinden (Gerfen et al. Sadikot et al. cholinergic neuromodulation is probably less prominent in these regions. Herkenham & Pert 1981. 1990). these striatal regions (Figure 1e) are anatomically and functionally distinct in both rodents and primates ( Joel & Weiner 1994. Compartments Under the light microscope. 1985) and somatostatin (Gerfen 1984). Given the apparent lack 130 Kreitzer of cholinergic markers in the patch.org by University of Manchester . The ventral striatum. descending motor axon bundles perforate the striatum. with distinct properties from both the dorsomedial and the dorsolateral striata (Nicola 2007).

For personal use only. 2009. Although some of these terminals are found directly adjacent to cortical synapses at spine necks (Freund et al. Midbrain DA neurons are spontaneously active at low frequencies (1–8 Hz) in vivo.18 μm (Arbuthnott & Wickens 2007). dopaminergic tone can be modulated on longer timescales in response to behavioral states including uncertainty. The axons of DA neurons arborize extensively in the striatal neuropil (Prensa & Parent 2001). The striatum is densely innervated by dopaminergic fibers originating in the SNc (dorsal striatum) and ventral tegmental area (ventral striatum). 1994). In response to behaviorally relevant stimuli (Schultz 2007a). striatal regions differ in several other important aspects. and striatal MSNs. www. These phasic spikes of DA are capable of activating lower-affinity Gs -coupled dopamine D1-type receptors (D1. However. Wu and Parent 2000). 2007). GABAergic interneurons. Consistent with this hypothesis. it is clear that DA reuptake mechanisms are not robust enough to limit spillover away from release sites. Schultz 2007b). most DA receptors are located extrasynaptically (Yung et al. 1995). most likely by activating high-affinity Gi coupled dopamine D2-type receptors (D2–D4) (Richfield et al. 1989). In addition. In addition to their connectivity. but not dorsomedial striatum (Herkenham et al.org • Striatal Physiology and Pharmacology 131 Annu. giving rise to a dense matrix of en passant terminals capable of releasing DA over large regions of striatum. with higher densities in the medial striatum and the ventral striatum (Gerfen et al. Rev. This firing maintains a tonic DA tone that is critical for normal striatal function (Schultz 2007b). Nicola et al. In addition. cannabinoid CB1 receptors are highly expressed in ventral and dorsolateral striatum. STRIATAL NEUROMODULATORS Dopamine DA plays a fundamental role in normal basal ganglia function and movement (Heien & Wightman 2006.annualreviews. or reward (Schultz 2007a). dopaminergic neurons fire bursts of action potentials that briefly elevate striatal extracellular DA.annualreviews. a separate midbrain nucleus adjacent to the SNc (Fields et al. Dopaminergic boutons represent nearly 10% of all striatal synapses (Groves et al. D5) (Richfield et al. 1989). stress. whereas calbindin is highly expressed in dorsomedial striatum but only weakly expressed in dorsolateral striatum (Gerfen et al. . Smith et al. 1984. In contrast. Striatonigral and striatopallidal MSNs contain transcripts for both D1. in contrast to rodents (Wu & Parent 2000). 1994). 1985). Striatal region gene expression patterns also differ. DA receptors are present in every cell type in the striatum. 1990). primates have more calretinin-positive interneurons and also exhibit greater densities of parvalbumin-positive interneurons in the dorsomedial striatum.org by University of Manchester . where they have been linked to modulation of dendritic conductances and synaptic integration (Nicola et al. Downloaded from www. with 10%–20% overlap of D1 and D2 receptor transcripts (Surmeier et al. 1993). Neurosci. 2000). receives glutamatergic inputs from frontal cortex and limbic regions (Brog et al.32:127-147. 2000. and shell regions are more similar to the amygdala (Zahm 2000). For example. and the nearest-neighbor distance between dopaminergic boutons is only ∼1. 1991). the dopaminergic innervation of the ventral striatum derives from the ventral tegmental area. including cell-type prevalence and gene expression patterns.and D2-class DA receptors.striatum. and cholinergic interneurons all express DA receptors. although different cell types express different DA receptor subtypes. 1985). 1985. The ventral striatum can be further subdivided into core and shell regions: Core regions display similarity to the dorsal striatum. Parvalbumin-positive (FS) interneurons are enriched in the lateral striatum and are much less evident in the medial striatum (Kita et al. somatostatin-positive (LTS) interneurons have a complementary distribution. suggesting that DA acts to some degree via volume transmission (Cragg & Rice 2004). Differences in regional density and prevalence are species specific: Primates exhibit a higher density of interneurons than do rodents (Graveland et al.John Rylands Library on 10/28/11.

2001). implying significant posttranscriptional control of DA receptor expression in MSNs. which are expressed widely 132 Kreitzer in the nervous system. but they can be classified into at least two types on the basis of their axonal projection patterns (Smith et al. acetylcholinesterase. In vivo. 2009. suggesting that this pause in cholinergic interneuron firing may be associated with behaviorally significant cues. Zhou et al. In contrast. 1997. mAChRs are expressed widely on MSNs.John Rylands Library on 10/28/11. nicotinic receptors are expressed mainly in presynaptic DA terminals and FS interneurons (Koos & Tepper 2002. cholinergic interneurons exhibit tonic low-frequency activity (<10 Hz) that is transiently inhibited in response to visual or auditory cues associated with movement tasks (Aosaki et al. Rivera et al.32:127-147. Weiner et al. striatopallidal MSNs send axons to the GP. and GABAergic interneurons. All MSNs share a similar morphology. 2002). 1998). 2002). Yan & Surmeier 1997). particularly in presynaptic terminals where they can enhance neurotransmitter release (Zhou et al. 1994a. 2004). 1984. Rev. Matsumoto et al. 1990). Yan et al. Immunohistochemical and functional evidence indicates that striatal GABAergic interneurons express primarily D5 receptors (Centonze et al. 2001). M1. 1996). as well. MEDIUM SPINY NEURONS Membrane Properties The principal neurons of the striatum are the MSNs. M1 receptors are expressed in all MSNs. Zhou et al. although there is some evidence for expression on glutamatergic terminals. Although cholinergic interneurons constitute less than 1% of all striatal neurons (Rymar et al. However. Kimura 1986). All five muscarinic receptor subtypes (M1–M5) are expressed in the dorsal striatum. M3.org by University of Manchester . 1992. 1997. This class of afferents project . The pause appears to require coordinated synaptic inputs from both the SNc and intralaminar thalamic nuclei (Aosaki et al. Apicella et al. The extent of D3–D5 receptor expression in MSNs remains unclear. Striatopallidal MSNs appear to receive a bulk of the sensorimotor corticostriatal afferents (Berretta et al. Nicotinic receptors are pentameric ligandgated ion channels. However. 1991. Annu. which may serve to limit ACh diffusion. 2000. ACh is rapidly degraded by an efficient extracellular enzyme. their dense and extensive axonal arborization ensures widespread release of ACh. ACh acts at both nicotinic (nAChR) and muscarinic (mAChR) receptors in the striatum. thus only indirectly connecting to basal ganglia output nuclei through a polysynaptic pathway. although the precise mechanisms have yet to be determined (Bennett & Wilson 1998). 2004). Schwartz et al. cholinergic interneurons.annualreviews. Yan & Surmeier 1996). In contrast. which is released into the extracellular space by tonically active cholinergic interneurons (Bolam et al. Neurosci. Striatonigral MSNs project directly to basal ganglia output nuclei: internal globus pallidus (primates)/entopeduncular nucleus (rodents) and the SNr. whereas cholinergic interneurons express both D2 and D5 receptors (Yan et al. In contrast. Parthasarathy & Graybiel 1997). In the striatum. M2 receptors are found exclusively in cholinergic interneurons (Bernard et al. Rymar et al. immunohistochemical studies indicate only a 1% overlap between D1 and D2 (Ince et al. 1995.1996). whereas M4 receptors are restricted to direct-pathway MSNs (Ince et al. 2002). which represent >95% of all striatal neurons and form the sole output to downstream basal ganglia nuclei (Kemp & Powell 1971a. 1990). 2001. For personal use only. which like DA may act locally on MSN synapses (Izzo & Bolam 1988) and have a more widespread influence via volume transmission (Contant et al. 1997. Downloaded from www. 2003a. and M5 receptors are Gq -coupled. where—along with M4 receptors—they function as cholinergic autoreceptors regulating ACh release (Alcantara et al. whereas M2 and M4 receptors are Gi -coupled. 1984. 1997). 2002). Acetylcholine ACh represents a second major striatal neuromodulator (Calabresi et al. Wilson et al.

topographically from cortex to the striatum. Neurosci. which can activate both small. Surmeier et al. Nisenbaum et al. 2004). as well as by several types of potassium conductances that shape their characteristic firing patterns (Nisenbaum & Wilson 1995) (Figure 2a). and a long delay to initial spiking. Shen et al. 1989). c LTS d TAN Figure 2 Firing properties of striatal neurons. 1996. www. Tkatch et al. LTS interneurons (c) have high input resistance and a sustained plateau potential that persists after the end of current injections. 1996. 1998.32:127-147. which together yield a slow depolarization and delay to the initial spike (Nisenbaum et al. 1991. 1998). 1999) and limit MSN firing rates. they do share a number of physiological properties. Rev. 1984). Tonically active cholinergic interneurons (TANs) (d ) exhibit a prominent hyperpolarization-activated current and broad spikes with long spike afterhyperpolarizations. and rapid membrane time constants (Mermelstein et al. At rest. and a vast majority of studies have considered them as a single cell type. Additionally. low input resistance. inward rectification. a reduction in available Kirs in a 20 mV 100 ms MSN b FS Annu. 2000). An early hint that MSN subtypes might exhibit different physiological properties came from studies of Kirs in striatopallidal and striatonigral MSNs of the nucleus accumbens (Mermelstein et al. both classes of MSNs receive synapses from interneurons as well as axon collaterals from other MSNs (Tepper et al. 2009. Uchimura et al. Downloaded from www. FS interneurons (b) have low input resistance and a characteristic rapid firing pattern. projections from neighboring barrels in mouse somatosensory cortex are targeted to discrete neighboring regions of striatal neuropil (Wright et al.2) A-type potassium currents. Given the hyperpolarized resting potential of typical MSNs.(Kv4.2) and slowinactivating (Kv1. 2005. Whole-cell current-clamp recordings were performed from different striatal cell types. Membrane depolarization inactivates Kirs and activates both fast. inwardly rectifying potassium channels (Kirs) contribute to their negative resting potential.org • Striatal Physiology and Pharmacology 133 . MSNs are characterized by their hyperpolarized resting membrane potential and low input resistance (Kita et al. For personal use only.annualreviews.and large-conductance calcium-activated potassium channels (Bargas et al. MSNs (a) exhibit low input resistance. By using post hoc reverse-transcriptase polymerase chain reaction (RT-PCR) analysis to identify MSN subtypes. for example. Although MSNs do not represent a homogenous population. 1989. 1999). 2004.John Rylands Library on 10/28/11. Depolarization and spiking also yield calcium influx. LTS interneurons also display rebound spiking following hyperpolarizations (not shown here). striatopallidal MSNs were found to exhibit Kir currents that inactivated more readily at hyperpolarized potentials.org by University of Manchester .annualreviews. as well as a persistent potassium conductance (Kv7).

Up and Down states in MSNs arise from the intrinsic membrane properties of MSNs as well as from the nature and coherence of excitatory synaptic drive from cortex and thalamus (Wilson & Kawaguchi 1996). which are activated in the Up state (Carter & Sabatini 2004) and are required for the induction of striatal long-term depression (Choi & Lovinger 1997. However. Activation of D1 receptors reduces sodium currents (Schiffmann et al. In addition to differences in Kir inactivation properties. Spiking was observed only during Up states. Up and Down States Early in vivo studies of striatal MSNs noted irregular rhythmic firing patterns that were accompanied by membrane potential shifts from hyperpolarized potentials (−90 to −70 mV) to more depolarized potentials (−60 to −40 mV) (Wilson & Groves 1981). Up states correlated among striatal MSNs. Kir properties in striatopallidal MSNs contribute to their increased excitability. Calcium-permeable AMPA receptors: GluR2-lacking receptors that exhibit calcium permeability and strong inward rectification that arises from block by intracellular polyamines at depolarized potentials striatopallidal MSNs could significantly increase their excitability. and even quiescent MSNs exhibited subthreshold membrane potential fluctuations. if sufficient numbers of glutamatergic inputs become active. Striatonigral MSNs express D1 receptors. For personal use only. Downloaded from www. Recent work indicates that Up and Down states are most prominent under anesthesia and during slow-wave sleep. 1995. Additionally.annualreviews. which were subsequently termed Down and Up states. Surmeier et al. although still present. and calcium channels. Rev. 2009. However. Neurosci. State transitions. The stability of MSNs at rest (Down state) is due to high levels of Kir that limit membrane depolarization in response to excitatory synaptic inputs. a more recent study using BAC transgenic mice found that striatopallidal MSNs fired at higher rates in response to current injections (Kreitzer & Malenka 2007). MSNs can be depolarized Kreitzer enough to block Kirs. are less obvious under these conditions (Mahon et al. At depolarized Up state potentials. although excitability differences persist even during large current injections that significantly depolarize MSNs and should block Kirs (Kreitzer & Malenka 2007). suggesting that other factors may be important. excitatory postsynaptic potentials are mediated almost entirely by AMPA receptors. MSNs express low-voltageactivated l-type calcium channels (Cav1. Neuromodulation Striatal MSNs exhibit numerous ionic conductances that shape their firing properties. 1992) and enhances Kirs (Pacheco-Cano et al. NMDA receptors are also activated. D1 receptors also enhance l-type currents that are activated in the Up state (Carter & Sabatini 2004. 1996). both of which are predicted to reduce MSN excitability. 2007). shifting MSNs into the Up state (Blackwell et al. In contrast. Kreitzer & Malenka 2005). 1998).John Rylands Library on 10/28/11.3). The Up state persists as long as sufficient excitatory drive is present to maintain depolarization. potassium. but blocked by intracellular polyamines at depolarized potentials Annu. 2006). Up state transitions also change the properties of synaptic conductances. Thus. consistent with the hypothesis that MSNs receive converging inputs from cortical neurons that fire in a correlated—but not totally synchronous—manner. which regulate sodium. The magnitude of the Up state shift is determined by voltage-sensitive potassium conductances that become activated following depolarization and serve to limit the extent of synaptically driven depolarization (Wilson & Kawaguchi 1996).org by University of Manchester . yielding slower excitatory potentials that summate more readily. 134 . although not every Up state yielded a spike. and many of these conductances are sensitive to neuromodulators such as DA and ACh.32:127-147.Inwardly rectifying potassium channels: a voltage-sensitive potassium channel that is permeable to potassium at hyperpolarized potentials. 2003). striatopallidal Kirs also display relatively greater inhibition by muscarinic M1 receptors than do striatonigral neurons (see below for further discussion) (Shen et al. although individual spikes did not (Stern et al. In the Down state. Up state transitions also shift the dominant source of synaptic calcium influx from calcium-permeable AMPA receptors to NMDA receptors (Carter & Sabatini 2004). the waking state is characterized by noisy MSN membrane fluctuations. Consistent with this finding.

yet they are critical for regulating striatal output. Downloaded from www. which is particularly sensitive to PIP2 depletion (Du et al. like D1 receptors. Further studies will be required to clarify this issue. which should facilitate Up state transitions. which are expressed by striatopallidal and striatonigral MSNs. although their particular role has been disputed. Rymar et al. INTERNEURONS Fast Spiking Interneurons FS interneurons represent only a few percent of all striatal neurons (Kita et al.32:127-147. D2 receptors may reduce the excitatory drive necessary for Up state transitions on a timescale of seconds. 1990). D1 receptors facilitate the firing of striatonigral MSNs. 2007).John Rylands Library on 10/28/11. if excitatory synaptic drive Annu. Yin & Lovinger 2006). It is intriguing to note that D2 receptors. M1 activation in striatal MSNs also facilitated depolarization-evoked endocannabinoid release (Narushima et al.3 expression. M1 activation also blocks a persistent potassium current mediated by Kv7 channels (Shen et al. Moreover. In contrast. leading to enhanced spiking. A-type potassium currents are partially activated. inhibit www. In the hippocampus and cerebellum. these findings suggest that D1 receptor activation acts as a filter to limit Up state transitions to periods of significant excitatory drive. these findings indicate that M1 activation increases MSN excitability and also enhances the likelihood of state transitions in striatopallidal MSNs. This modulation is selective for striatopallidal MSNs because of their high level of Kir2. Striatopallidal MSNs exhibit high levels of D2 receptor expression and prominently express a form of endocannabinoid-dependent long-term depression of glutamatergic synapses (Kreitzer & Malenka 2007). 1998). 1999. Neurosci. once in the Up state. 2005). However. M1 activation inhibits N. 2007). they also inhibit l-type currents and reduce spiking in the Up state (Hernandez-Lopez et al. 2009.and P/Qtype calcium channels that couple to calciumactivated potassium channels in MSNs. 1995).org by University of Manchester . which should also enhance firing in the Up state (Nisenbaum et al. mainly inhibit MSN firing. giving rise to an enhancement of firing when neurons are depolarized (Hernandez-Lopez et al. which will tend to keep MSNs hyperpolarized. M1 receptors have also been linked to endocannabinoid production in MSNs. Thus. Cholinergic modulation of MSNs is mediated by muscarinic ACh receptors (Yan et al. activation of Gq coupled receptors such as M1/3 or mGluR1/5 stimulates endocannabinoid production via phospholipase Cβ. 2004). Rev. which represent a class of lipophilic membrane-derived signaling molecules produced in neurons in response to elevations of intracellular calcium and PLC activation (Piomelli 2003). However. Mice with decreased numbers of striatal FS neurons exhibit procedural learning deficits (Marrone et al. 2006). Furthermore. Thus. For personal use only. Activation of M1 receptors. D2 receptors. when MSNs are in the Down state. shifts the activation and inactivation of transient A-type potassium currents to more hyperpolarized potentials (Akins et al. D1 receptors block a slowly inactivating potassium conductance. Together.org • Striatal Physiology and Pharmacology 135 .annualreviews. while increasing the requirement for synchrony on the milliseconds timescale to drive spiking. 2006). Although they reduce Kir currents (Uchimura & North 1990). 2004). 1990. exhibit opposite effects in the Down and Up states. which are expressed at high levels in striatopallidal MSNs. 1997). M1 receptor activation inhibits Kirs via phospholipase C activation and depletion of phosphatidylinositol biphosphate (PIP2 ) (Shen et al. a different study concluded that M1 receptor activation might actually inhibit endocannabinoid release via inhibition of l-type voltage-sensitive calcium channels in MSNs (Wang et al. Striatal D2 receptors have also been linked to mobilization of endocannabinoids (Giuffrida et al. However. 2005).annualreviews. however. 2001).Surmeier et al. 2000). can overcome these currents and shift MSNs into the Up state. then these A-type potassium currents will also inactivate more readily and reduce delays to spiking. Together. and injections of GABAA antagonists into the putamen increase MSN firing (Mallet et al.

which receive small numbers of inputs from large numbers of afferents. In vivo. FS interneurons exhibit higher firing frequencies than do MSNs and may entrain oscillations between cortex and striatum (Berke et al. even bursts in single interneurons can significantly delay spiking in MSNs (Koos & Tepper 1999). LTS interneurons represent a few percent of striatal neurons (Rymar et al. Kubota et al. LTS interneurons are innervated by glutamatergic afferents from both cortex and thalamus. 1998). FS interneurons have faster response latencies than do MSNs in vivo and may limit the duration of MSN spiking. and nitric oxide synthase (Chesselet & Graybiel 1986. Unlike MSNs. 2005) owing to both a reduced excitatory drive on MSNs and an increased inhibitory tone. Thus. Thus. where they form numerous proximal synapses capable of inhibiting the generation of action potentials in MSNs (Bennett & Bolam 1994. 1995). They are relatively enriched in dorsolateral striatum (Bennett & Bolam 1994. Koos & Tepper 1999). ACh also excites FS interneurons through a direct depolarization mediated by nondesensitizing nicotinic receptors. 1989).32:127-147. Striatal FS interneurons share properties similar to FS interneurons in the hippocampus and cortex. 1991). Vuillet et al. Given the prominent role of FS interneurons in regulating MSN spiking. Koos & Tepper 1999. 2004). For personal use only. Kita et al. 1990) (Figure 2b). FS interneurons display dendritic gap junctions and exhibit electrotonic coupling (Kita et al. ACh may also indirectly facilitate FS firing by enhancing DA release via presynaptic nicotinic receptors (Zhou et al. However. Vuillet et al. 2002) and thalamus (Sidibe & Smith 1999) and receive inhibitory inputs from other interneurons (Chang & Kita 1992) and a population of globus pallidus neurons (Bevan et al.org by University of Manchester . 1999). Low-Threshold Spiking Interneurons A second type of GABAergic striatal interneuron is the LTS cell. Ramanathan et al. Lapper et al. elevations in ACh are predicted to excite FS interneurons directly. and induce dystonia (Yamada et al. and in turn form synapses onto MSNs (Sidibe & Smith 1999. FS interneurons often receive multiple synaptic contacts from individual afferent fibers (Ramanathan et al. they do not require the same degree of input synchrony that MSNs need to trigger a spike. 1990. Neurosci. Kita et al. 136 Kreitzer Annu. This influence arises from the presence of multiple synaptic contacts on MSNs. 2005). Mallet et al. Kita 1993. 2003b) and also via D2-mediated inhibition of GABAergic afferents onto FS interneurons (Bracci et al. modulation of their firing properties by neuromodulators should be important for striatal function. elevated DA would directly excite FS interneurons but simultaneously inhibit cholinergic interneurons (see below). which can lead to firing synchrony among local interneuron populations. such as short-duration spikes. Centonze et al. neuropeptide Y. DA excites FS interneurons via D5 receptor activation (Bracci et al. FS interneurons receive excitatory synapses from both cortex (Kita 1993. 2004) and exhibit fewer dendritic branches. Smith & Parent 1986. FS interneurons mainly target MSNs. In addition. 2002). as well as less dense and more extensive axonal arborizations relative to FS interneurons (Kawaguchi 1993.John Rylands Library on 10/28/11. MSN synapses onto interneurons were not observed. 1995. which could mitigate DA-mediated FS excitation to some degree.spiking in the SNr (Yamada et al. 2009. high-frequency firing. and gap junctions with other FS interneurons (Kawaguchi 1993. 2002). suggesting that they play a key role in sensorimotor integration. whereas a single interneuron connects to 135–541 MSNs (Koos & Tepper 1999). 1990). . 2002. as well as from their proximal location on MSN somata and dendrites (Kubota & Kawaguchi 2000). 1992. Desynchronized cortical activity enhances interneuron spiking and leads to a dramatic reduction in MSN spiking activity (Mallet et al. Researchers estimate that a single MSN receives inhibitory synapses from 4–27 FS interneurons. Rev. Like FS interneurons. 2002). which likely plays a role in the induction of striatal long-term plasticity (Calabresi et al.annualreviews. Downloaded from www. 1983). Vincent et al. 1993. Yoshida et al. In contrast. LTS interneurons express somatostatin.

1994.Annu. Thus. but also on FS interneurons (Chang & Kita 1992. 1998). leading to significant increases in spiking (Centonze et al. Wilson et al. Modulation of striatal interneurons has not been well characterized. constitute only 1%–2% of striatal cells (Kemp & Powell 1971a). A characteristic feature of cholinergic interneurons in vivo is their pause in tonic firing in response to salient cues.annualreviews. which have not been well characterized (Bennett & Bolam 1993. Cholinergic interneurons receive only sparse excitatory innervation. M2 receptors may also function as presynaptic autoreceptors (Hersch et al. 2004). Cholinergic interneurons fire spontaneously in vivo owing to their expression of sodium currents and hyperpolarization-activated cation currents (Bennett et al. Neurosci. 1993. Muscarinic M1 and M2 receptors are also expressed in LTS interneurons (Ariano & Kenny 1989. and these serve to amplify and prolong the effects of hyperpolarizing inputs (Wilson 2005). Kubota et al. Electrophysiologically. Muscarinic M2 and M4 receptors. express Kirs that become unblocked at hyperpolarized potentials. 1994a.32:127-147. the cortex (Thomas et al. 2002). as well as M2 and M4 mAChRs (Bergson et al. A second population of LTS interneurons may correspond to calretininpositive interneurons. but their physiological roles remain unknown. Activation of these receptors depolarizes LTS interneurons. D1-type and D2-type dopamine receptors exert opposite effects on excitability within individual cholinergic interneurons. Wilson & Goldberg 2006).John Rylands Library on 10/28/11. 1994b. Cholinergic Interneurons Cholinergic interneurons. 1998). in addition. 1984. Levey et al. Phelps et al. They also receive inhibitory synapses from MSNs (Bolam et al. but their influence is significant. which form synapses primarily on MSNs (Bolam et al. D5 receptor activation depolarizes cholinergic interneurons through a cAMP-dependent mechanism (Aosaki et al. including reward and reward prediction (Aosaki et al. Hersch et al. 1994) regulating ACh release via direct Gβ/γ-mediated inhibition of presynaptic calcium channels (Yan & Surmeier 1996). 1995. 2009. 2004). these interneurons display higher input resistances and relatively depolarized resting potentials (Kawaguchi 1993) (Figure 2c). whereas D2 signaling mediates an inhibition of voltage-sensitive sodium channels that reduces excitability (Maurice et al. 1990. LTS interneurons are characterized by their plateau potentials and low-threshold spikes. 1993). Cholinergic interneurons. reduce excitability albeit through a different mechanism involving activation of a potassium conductance (Calabresi et al. They have large (20–50 μm diameter) cell bodies and widespread axonal fields. Bernard et al. like other striatal interneurons. express D5 receptors (Rivera et al. 2002). 2000). However. The instrinsic properties of cholinergic interneurons are also critical. Downloaded from www. LTS interneurons. 1998).org • Striatal Physiology and Pharmacology 137 . Morris et al. 1985). Graybiel et al. like MSNs. 1989). Rev. although the precise signaling mechanisms are not clear. www. Cholinergic interneurons express both D2 and D5 receptors. Although the precise origins of this pause are still unclear. 2000). Koos & Tepper 2002). although their innervation by dopaminergic axons is prominent in both dorsal and ventral striata. 2001). which derives primarily from the thalamus (Lapper & Bolam 1992) and. For personal use only. 1988). 1992. also known as large aspiny neurons or tonically active neurons. to a lesser extent. Cholinergic interneurons can be electrophysiologically distinguished by their depolarized resting potential and highinput resistance (Kawaguchi 1993) (Figure 2d ).org by University of Manchester . Tepper & Bolam 2004) but appear to lack significant thalamic innervation (Sidibe & Smith 1999). 1994. like D2 receptors. Izzo & Bolam 1988. some LTS interneurons also appear to receive significant dopaminergic innervation (Hidaka & Totterdell 2001. owing primarily to calcium-activated potassium channels (Kawaguchi 1992. Matsumoto et al.annualreviews. 1986). Their firing rates are limited to 2–10 Hz by a prominent afterhyperpolarization following each spike. it requires both intact thalamic and dopaminergic innervation to occur (Aosaki et al.

138 Kreitzer reduced autoinhibition of ACh release might compensate to some extent for this reduction in cholinergic tone. Rev. given its relatively higher affinity for DA (Richfield et al. FS and LTS interneurons are depicted in blue and red. In addition to differences in synaptic convergence. Schematic depicting different types of striatal neurons and their complement of dopamine and acetylcholine receptors. as well as on DA and ACh release itself. 2009. and subsequent reductions in cholinergic tone. Similarly. Neurosci.annualreviews. increased dopaminergic tone is predicted to increase D2 receptor activation selectively. Excitability of both FS and LTS interneurons would be increased. respectively.nAChR D5 s D2 i D1 M1 q M1 q s i M4 FS Indirect MSN Direct MSN D5 M4 M2 i D2 i i D5 s Annu. changes in ACh or DA levels will exert complex effects on striatal neuron activity. For example. and the cholinergic neuron is shown in green. G protein–coupled receptors are displayed with their associated G-protein: Gs (magenta). Reduced depolarization of FS interneurons via nicotinic receptors would also occur. For personal use only.32:127-147. Downloaded from www. intrinsic membrane properties. Thus. FS interneurons also express the ionotropic nicotinic ACh receptor. whereas striatopallidal MSNs would be inhibited. Large increases in DA yield both D1 and D2 receptor activation. However. brief spikes in DA concentrations could exert significantly different effects. reduced activation of presynaptic nicotinic receptors on dopamine terminals would reduce DA release itself. Gi ( purple). 1989). decreased cholinergic interneuron activity. and in vivo firing patterns.John Rylands Library on 10/28/11.org by University of Manchester . CONCLUSIONS Significant heterogeneity exists within both interneuron and projection neuron populations in the striatum. This would lead to decreased striatopallidal MSN output. In contrast. rendering them less excitable. each type of striatal neuron expresses a distinct complement of DA and ACh receptors (Figure 3). yielding more powerful feedforward inhibition and increased temporal precision of MSN . striatonigral MSN output would be enhanced. Striatopallidal (indirect-pathway) and striatonigral (direct-pathway) MSNs are shown in gray. M1 q s i M2 LTS TAN Figure 3 Dopaminergic and cholinergic modulation of striatal neurons. Thus. and the system would reestablish an equilibrium level of DA and ACh. or Gq (blue).

annualreviews. Given the diversity of striatal neurons and their responses to various neuromodulators. 2006). Penney JB. whereas neighboring striatonigral MSNs retain normal morphology (Day et al. Muscarinic modulation of a transient K+ conductance in rat neostriatal neurons. 1998. J. 12:366–75 Alcantara AA. Dopamine D1-like receptor activation excites rat striatal large aspiny neurons in vitro.Annu. DISCLOSURE STATEMENT The author is not aware of any affiliations. striatal interneurons are selectively spared (Cicchetti et al. nitric oxide. Future studies will be required to understand how these various factors interact to regulate basal ganglia circuit function. Neurosci. striatopallidal MSNs are selectively vulnerable to cell death (Mitchell et al. Our research on this subject is supported by the Pew Charitable Trusts.annualreviews. 434:445–60 Aosaki T. memberships. Neurol. and The J. 1990. 2001. At the same time. 1995. David Gladstone Institutes. Kitai ST. Science 265:412–15 Aosaki T. Interestingly. Trends Neurosci. the physiological properties of striatal neurons also depend on the properties of their synaptic inputs. 1985). Kiuchi K. 73:1234–52 Aosaki T. J. and various neuropeptides play important roles in shaping the physiology of striatal neurons. The functional anatomy of basal ganglia disorders. Surmeier DJ. striatopallidal MSNs exhibit increased firing rates (Mallet et al. Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys. Neurosci. 1999. ACKNOWLEDGMENTS I thank members of my laboratory for their critical reading of the manuscript and Carlo Tringale for administrative assistance. Mrzljak L. In addition. 1994a. However. 1989. J. Young AB. LITERATURE CITED Akins PT. a host of other neuromodulators including adenosine. Kimura M. although both types of MSNs eventually degenerate. the CHDI Foundation. spiking output. Comp. The increased prevalence of interneurons in Huntington disease could exacerbate striatal deficits arising from loss of MSNs (Cepeda et al. endocannabinoids. Kawaguchi Y. 2006). Hersch SM. 2009. Neurophysiol. Temporal and spatial characteristics of tonically active neurons of the primate’s striatum. Graybiel AM.org • Striatal Physiology and Pharmacology 139 . funding. Ferrante et al. which suggests that this decrease in spine density may reflect a compensatory mechanism aimed at reducing overexcitation. Rev. 1996. Reiner et al. Kimura M.32:127-147.John Rylands Library on 10/28/11. Graybiel AM. Heterogeneity among neuronal populations is therefore a critical factor to consider when studying striatal function. 18:5180–90 www. Downloaded from www. In contrast. Recent evidence indicates that striatopallidal MSNs undergo spine loss following dopamine depletion. it is also apparent that significant caution is required in experimental design and data interpretation when performing pharmacological manipulations in the intact striatum. For personal use only. In Huntington disease.org by University of Manchester . Cholinergic interneurons would exhibit more complex changes owing to the opposing actions of simultaneous D2 and D5 receptor activation. Muscarinic m1 and m2 receptor proteins in local circuit and projection neurons of the primate striatum: anatomical evidence for cholinergic modulation of glutamatergic prefronto-striatal pathways. 1988). diseases of the striatum such as Parkinson disease and Huntington disease selectively affect particular neuronal subtypes. Jakab RL. or financial holdings that might be perceived as affecting the objectivity of this review. 2004). Levey AI. Goldman-Rakic PS. Nature 344:240–42 Albin RL.

Vilchis C. et al. Izzo PN. Skurski J. Normand E. Brain Res. 1993. Neurosci. Regional. Downloaded from www. J. and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. Anat. Neuron 43:883–96 Bernard V. 497:51–58 Bargas J. Neurosci. Standaert DG. 2007. Li Y. Brain Res. Bolam JP. J. Blood AJ. Smiley JF. Goldman-Rakic PS. 30:62–69 Ariano MA. Selective innervation of neostriatal interneurons by a subclass of neuron in the globus pallidus of the rat. Czubayko U. Galarraga E. Quantitative estimate of synaptic inputs to striatal neurons during up and down states in vitro. 15:7821–36 Berke JD. Laribi O. Rev. Parthasarathy HB.org by University of Manchester .John Rylands Library on 10/28/11. Neurophysiol. Centonze D. Rev. 1986. Bloch B. Brain Res. Rye DB. 609:137–48 Bennett BD. 1998. Booth PA. 2003. cellular. 1995. Hanson PI. Levey AI. Eaton SA.Aosaki T. Space. Okatan M. 84:672–75 Arbuthnott GW. 18:9438–52 Blackwell KT. Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. Synaptic regulation of action potential timing in neostriatal cholinergic interneurons. 9:222–34 Brog JS. J. 2002. Neurosci. Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons. Graybiel AM. 1991. Ca2+ -activated outward currents in neostriatal neurons. Bolam JP. 2009. Schultz W. Neurosci. 2004. 1998. Synaptic organisation of the basal ganglia. Levenson R. 18:10207–18 Bernard V. 1994b. Neuroscience 62:707–19 Bennett BD. Oscillatory entrainment of striatal neurons in freely moving rats. Scarnati E. 17:4752–63 Bevan MD. Synaptic input and output of parvalbumin-immunoreactive neurons in the neostriatum of the rat. J. 338:255–78 140 Kreitzer Annu. J. A combination of choline acetyltransferase immunocytochemistry. Substance P-containing terminals in synaptic contact with cholinergic neurons in the neostriatum and basal forebrain: a double immunocytochemical study in the rat. J. 397:279–89 Bolam JP. 1994. Eichenbaum HB. Neuroscience 88:479–88 Bennett BD. 1998. 23:9123–32 Bolam JP. Levey AI. Wilson CJ. Tsubokawa H. Neurosci. 1992. J. Ishida A. 196(Pt. Neurosci. 1997. Kimura M. 1999. Local release of GABAergic inhibition in the motor cortex induces immediate-early gene expression in indirect pathway neurons of the striatum. Trends Neurosci. Responses of tonically active neurons in the primate’s striatum undergo systematic changes during behavioral sensorimotor conditioning. Ingham CA. Dopamine excites fast-spiking interneurons in the striatum. Neurosci. The pathophysiological basis of dystonias. Characterization of calretinin-immunoreactive structures in the striatum of the rat. Smith AD. For personal use only. Salyapongse A. Pineda JC. 87:2190–94 Breakefield XO. Watanabe K. J. 1984. Graybiel AM.32:127-147. 2000. time and dopamine. Graybiel AM. Cellular substrate of the histochemically defined striosome/matrix system of the caudate nucleus: a combined Golgi and immunocytochemical study in cat and ferret. 2000. Zahm DS. 14:3969–84 Apicella P. Deutch AY. Bolam JP. Bloch B. 12:3591–600 Berretta S.annualreviews. Mrzljak L. Plenz D. The patterns of afferent innervation of the core and shell in the “accumbens” part of the rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold. Neurosci. Booth PA. Calabresi P. Golgi-impregnation and electron microscopy. Wickens J. 4):527–42 Bolam JP. Pappy M. 1989. Wainer BH. Characterization of cholinergic neurons in the rat neostriatum. 1988. Striatal muscarinic receptors are associated with substance P and somatostatin containing neurons. Wilson CJ. J. Neurol. 20:8493–503 Bennett BD. Callaway JC. Bevan MD. Ayala GX. Subcellular redistribution of m2 muscarinic acetylcholine receptors in striatal interneurons in vivo after acute cholinergic stimulation. Neurosci. Kenny SL. Exp. J. 2008. 18:8539–49 Bergson C. . Comp. 1993. Hallett M. Tonically discharging neurons of monkey striatum respond to preparatory and rewarding stimuli. Hanley JJ. J. Neuroscience 24:853–75 Bolam JP. Neurosci. Neurosci. Nat. Bernardi G. Brain Res. Neuroscience 12:711–18 Bracci E. J. Izzo PN.

5-bisphosphate determine regulation of kir channels by diverse modulators. Gould PV. et al. 15:2049–52 Centonze D. Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum. Trends Neurosci. Gubellini P. Neurosci. J. Wu N. Neuroscience 17:547–71 Choi S. 23:8506–12 Centonze D. J. 365:397–403 Du X. Centonze D. Nicola SM. Parent A. 1984. Annu. et al. J.org by University of Manchester . J. Sabatini BL. Neurosci. 279:37271–81 Ferrante RJ. Heizmann CW. 1996. 23:6245–54 Cepeda C. Nguyen OK. Downloaded from www. Ingham CA. Gubellini P. Annu. J. Emson PC. Bernardi G. Kaneko T. Starling AJ. North RA. Trends Neurosci. Bernardi G. Bernardi G. Wilson CJ. Neurosci. Rev. Neurol. et al. Neurosci. 2):421–27 Calabresi P. Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons. Physiol. Richardson EP Jr. Natl. et al. Neurosci. 13:281–85 Donoghue JP. A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Descarries L. 2003a. 2004. Sparing of striatal neurons coexpressing calretinin and substance P (NK1) receptor in Huntington’s disease. Martin AB. Logothetis DE. 78:855–67 Chang HT. Pisani A. Ding J. Neurosci. Bird ED. Powell JF. Activation of dopamine D1-like receptors excites LTS interneurons of the striatum. Selective sparing of a class of striatal neurons in Huntington’s disease. 1984. State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. 1986. 1985. Sancesario G. Parvalbumin-containing GABAergic interneurons in the rat neostriatum. 1990. Pisani A. 1992. Proc. J. 2000. Nature 311:461–64 Gerfen CR. 1997. Eur. Trends Neurosci. Rice ME. 2006. with particular reference to dendritic spines. Morello M.annualreviews. Bracci E. .32:127-147. 1985. Science 230:561–63 Fields HL. Neurosci. Calabresi P. Kita H. Chem. Rohacs T. J. Primate models of movement disorders of basal ganglia origin. et al. Centonze D. Graybiel AM. Usiello A. An X. Increased GABAergic function in mouse models of Huntington’s disease: reversal by BDNF. Pisani A. 302:197–205 Cragg SJ. Neostriatal projections from individual cortical fields conform to histochemically distinct striatal compartments in the rat. Grande C. Margolis EB. 2003b.org • Striatal Physiology and Pharmacology 141 Annu. J. 574:307–11 Chesselet MF. Gubellini P. Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models. 2007. Rev. J. Eur. Brain Res. Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons. Neurosci. 510(Pt. Zhang H. Beal MF.Calabresi P. Smith AD. Compartmental organization of projections from the striatum to the substantia nigra in the rat. Neurosci. Watkins KC. Gubellini P. Nakamura K. 1986. Lopes C. 30:289–316 Freund TF. 9:251–59 DeLong MR. DAncing past the DAT at a DA synapse. Unzai T. Wang Z. 2009. Neurol. Grande C. Gubellini P. Sci.annualreviews. I. 236:454–76 Gerfen CR. Herkenham M. Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. 15:285–320 www. 1999. 23:120–26 Calabresi P. 2004. Mirshahi T. Martin JB. 2002. 2006. The neostriatal mosaic. Saulle E. 24:2813–24 Gerfen CR. Kowall NW. 27:270–77 Day M. 2004. Neurosci. Garcia S. Muscarinic IPSPs in rat striatal cholinergic interneurones. Centonze D. Decreased probability of neurotransmitter release underlies striatal long-term depression and postnatal development of corticostriatal synapses. Nat. USA 94:2665–70 Cicchetti F. Characteristic interactions with phosphatidylinositol 4. 19:2489–99 Carter AG. 1992. Brain Res. The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Nomura S. Neuroscience 71:937–47 Cowan RL. 1990. Acetylcholine-mediated modulation of striatal function. Acad. Umbriaco D.John Rylands Library on 10/28/11. Comp. Uzgil B. 730:232–37 Contant C. Neuron 44:483–93 Centonze D. Striatal neurons expressing somatostatin-like immunoreactivity: evidence for a peptidergic interneuronal system in the cat. Biol. Rev. Interneurons in the rat striatum: relationships between parvalbumin neurons and cholinergic neurons. Lovinger DM. J. Neuroscience 13:1189– 215 Fujiyama F. Comp. Hjelmstad GO. 2004. Res. Sancesario G. Brain Res. Ultrastructural characterization of the acetylcholine innervation in adult rat neostriatum. 1998. 1996. Erbs E. For personal use only. Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity.

Neurosci. 1978. Neurosci. Ultrastructural features of the nitric oxide synthase-containing interneurons in the nucleus accumbens and their relationship with tyrosine hydroxylase-containing terminals. Disord. 431:139–54 Hyman SE.org by University of Manchester . Neurol. 29:565–98 Ince E. Surmeier DJ. Williams RS. Nature 323:625–27 Graybiel AM. 1986. Neurol. Neuronal localization of cannabinoid receptors in the basal ganglia of the rat.Gerfen CR. 20:8987–95 Hersch SM. 2000. Flaherty AW. 1997. monkeys. Biol. Navarro M. parafascicular projections and acetylcholinesterase in rat striatum. Neurol. Piomelli D. Neurol. Rev. 1987. 2001. Annu. 1988. Levey AI. Parsons LH. 1994. 5-hydroxydopamine-labeled dopaminergic axons: three-dimensional reconstructions of axons. Ragsdale CW Jr.32:127-147. Rees HD. 1985. Doughty ML. Bolam JP. Downloaded from www. 1985. Linder JC. Aosaki T. The basal ganglia and adaptive motor control. Zheng C. Neurosci. Baughman RW. Neurosci. J. Drug Targets 5:99–108 Herkenham M. Kerr TM. Baimbridge KG. Pert CB. Acad. 1988. Neural mechanisms of addiction: the role of reward-related learning and memory. Rev. The neostriatal mosaic: compartmental distribution of calciumbinding protein and parvalbumin in the basal ganglia of the rat and monkey. Graybiel AM. D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLCβ1-IP3calcineurin-signaling cascade. Neurosci. 1981. 460:161–67 Giuffrida A. J. Gutekunst CA. J. Proc. 2008. Brain Res. Losos K. 72:369–86 Gong S. Proc. Brain Res. Galarraga E. D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an L-type Ca2+ conductance. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Eckenstein F. CNS Neurol. 2:358–63 Goldman PS. Richfield EK. Synapse 27:357–66 Izzo PN. Histochemically distinct compartments in the striatum of human. Neuroscience 23:223–42 142 Kreitzer Annu. The basal ganglia. Cholinergic synaptic input to different parts of spiny striatonigral neurons in the rat. Didkovsky N. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Perez-Garci E. Bargas J. Distribution of m1-m4 muscarinic receptor proteins in the rat striatum: light and electron microscopic immunocytochemistry using subtypespecific antibodies. de Costa BR. . et al. 234:317–33 Graybiel AM. 1999. 269:219–34 Jimenez-Castellanos J. Neurosci. Young SJ. Comp. 2003. Ciliax BJ. Natl. Comp. Totterdell S. Neurosci. USA 75:5723– 26 Groves PM. 17:3334–42 Hernandez-Lopez S. Wightman RM. Neuroscience 58:593–604 Heien ML. Annu. synapses and postsynaptic targets in rat neostriatum. An intricately patterned prefronto-caudate projection in the rhesus monkey. Galarraga E. Young WS 3rd. 1994. Lynn AB. et al. Miller JJ. Sci. 547:267–74 Herkenham M. USA 82:8780–84 Gerfen CR. 1977. 14:3351–63 Hidaka S. Sci. Habits. Tkatch T. Reyes A. and cat demonstrated by acetylthiocholinesterase staining. 2006. Levey AI. 2009. 2006. and the evaluative brain. Cholinergic neuropil of the striatum observes striosomal boundaries. Nat. Subdivisions of the dopamine-containing A8-A9-A10 complex identified by their differential mesostriatal innervation of striosomes and extrastriosomal matrix. Rev. J. Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Phasic dopamine signaling during behavior. Bargas J. DiFiglia M. Nature 291:415–18 Hernandez-Lopez S. J.annualreviews.John Rylands Library on 10/28/11. Curr. Mosaic distribution of opiate receptors. Rodriguez de Fonseca F. 31:359–87 Graybiel AM. A Golgi study of the human neostriatum: neurons and afferent fibers. and disease states. 10:R509–11 Graybiel AM. Nature 425:917–25 Graveland GA. 2000. Heilman CJ. reward. Kimura M. J. 1991. Comp. Comp. 1994. Acad. rituals. Nauta WJ. Science 265:1826–31 Graybiel AM. For personal use only. Differential expression of D1 and D2 dopamine and m4 muscarinic acetylcholine receptor proteins in identified striatonigral neurons. Malenka RC. Natl. J. Nestler EJ. 1997.

Wilson CJ. Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Malenka RC. 262:383–401 Kemp JM. 1992. Trans. 2:467–72 Koos T. Powell TP. Acad. Shimada S. 1993. 1993. For personal use only. Sci. Comp. 374:578–92 Kincaid AE. Weiner I. Trans. London B Biol. 458:389–93 Kubota Y. R. J. 1984. Passive electrical membrane properties of rat neostriatal neurons in an in vitro slice preparation. Corticostriatal innervation of the patch and matrix in the rat neostriatum. . Kita H.annualreviews. Sci. Brain Res. 580:215–24 Levey AI. Ballion B. 1998. 13:4908–23 Kawaguchi Y. J. 1994. Updyke BV. 99:51–72 Kita H. 1996. 1993. Okayama T. Philos. Rev. 1986. 1971b. Mikawa S. Large aspiny cells in the matrix of the rat neostriatum in vitro: physiological identification. Connectivity and convergence of single corticostriatal axons. 300:129–39 Koos T. Bolam JP. Sci. 1985. 2006. Neurosci. 1988. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Neuroreport 5:205–8 Kunzle H. 88:195–209 Lapper SR. Striatal interneurones: chemical. 1993. Inagaki S. Neurosci. 262:429–39 Kimura M. Brain Res. 2002. Neurosci. 1999. Neurosci. Slaght SJ. Proc. 1971a.org • Striatal Physiology and Pharmacology 143 Annu. Brain Res. Natl. et al. Cortical inputs and GABA interneurons imbalance projection neurons in the striatum of parkinsonian rats. London B Biol. Kawaguchi Y. Trends Neurosci. Neurophysiol. Nat. Res. Emson PC. Neurosci. Kito S. Prog. Input from the frontal cortex and the parafascicular nucleus to cholinergic interneurons in the dorsal striatum of the rat. Soc. Philos. Neurol. Le Moine C. Pezard L. et al. Powell TP. 1992. Soc. 2000. Neurosci. Tepper JM. Bolam JP. Projection of the digit and wrist area of precentral gyrus to the putamen: relation between topography and physiological properties of neurons in the putamen. 2009. J. 22:529–35 Kreitzer AC. 2006. Neostriatal GABAergic interneurones contain NOS. Physiological. 1995.org by University of Manchester . Brain Res. 67:1669–82 Kawaguchi Y. Dual cholinergic control of fast-spiking interneurons in the neostriatum. Neuropeptide Y-immunoreactive neurons receive synaptic inputs from dopaminergic axon terminals in the rat neostriatum. An autoradiographic study in Macaca fascicularis. Nature 445:643–47 Kubota Y. Brain Res. 18:4722–31 Kita H. Deniau JM. Kitai ST. Hersch SM. 339:245–55 Mahon S. Parvalbumin-immunoreactive neurons in the rat neostriatum: a light and electron microscopic study. Neurosci. Neuroscience 51:533–45 Lapper SR. and histochemical characterization of three classes of interneurons in rat neostriatum. Smith Y. Niznik HB. 26:3875–84 www. Vautrelle N. Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. Wilson CJ. 18:527–35 Kemp JM. Parent A. Neurosci. 2005. Sunahara RK. Heizmann CW. Neurosci. Cortical input to parvalbumin-immunoreactive neurones in the putamen of the squirrel monkey.32:127-147.John Rylands Library on 10/28/11. Brain Res. J.annualreviews. R. J. GABAergic circuits of the striatum. Kawaguchi Y. 20:375–86 Kubota Y. Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies. calretinin or parvalbumin. J. The structure of the caudate nucleus of the cat: light and electron microscopy.Joel D. 1975. Tepper JM. Dependence of GABAergic synaptic areas on the interneuron type and target size. Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. Brain Res. Neurosci. 1992. 3:436–43 Kincaid AE. The role of primate putamen neurons in the association of sensory stimuli with movement. Wilson CJ. 26:12587–95 Mallet N. Zheng T. Downloaded from www. USA 90:8861–65 Liles SL. Gonon F. The termination of fibres from the cerebral cortex and thalamus upon dendritic spines in the caudate nucleus: a study with the Golgi method. 2007. Malenka RC. et al. Sadikot AF. physiological and morphological characterization. J. Neuroscience 63:363–79 Kawaguchi Y. Kosaka T. 536:1–15 Kita T. Distinct patterns of striatal medium spiny neuron activity during the natural sleep-wake cycle. J. relation to the compartments and excitatory postsynaptic currents. Augood SJ. 1990. The organization of the basal ganglia-thalamocortical circuits: open interconnected rather than closed segregated. J. morphological. Rye DB. 25:10537–45 Kreitzer AC.

Bargas J. For personal use only.Mallet N. Chan CS. Altered cortico-striatal synaptic plasticity and related behavioural impairments in reeler mice. Bergman H. 44:283–88 Pacheco-Cano MT.) 191:521–50 Nicola SM. Brain Res. Fuxe K. Hazrati LN. 76:1180–94 Olson L. J. Functional anatomy of the basal ganglia. Selective blockade of a slowly inactivating potassium current in striatal neurons by (+/−) 6-chloro-APB hydrobromide (SKF82958). Surmeier DJ. Surmeier DJ. 21:7247–60 Ragsdale CW Jr. 1998. The fronto-striatal projection in the cat and monkey and its relationship to inhomogeneities established by acetylcholinesterase histochemistry. J. Brain Res. 17:2477– 91 Phelps PE. 110:205–11 Parent A. 2007. 2006. 1981. Galarraga E. Mercer J. 2001. Heterogeneity of striatal and limbic dopamine innervation: highly fluorescent islands in developing and adult rats. 1996. Comp. J. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Le Moine C. Synapse 29:213– 24 Nisenbaum ES. Neurosci. J. Neurosci. Houser CR. Neurosci. Neurosci. Foehring RC. 269:506–22 144 Kreitzer Annu. Vaughn JE. 15:4449–63 Nisenbaum ES. Neurobiol. et al. The nucleus accumbens as part of a basal ganglia action selection circuit. Graybiel AM. J. Song WJ. et al. Marinelli S. Tapia D. Neurosci. 27:496–506 Nicola SM. Wilson CJ. 1997. Tkatch T. 1999. Minamimoto T. Sgobio CA. Annu. Neurons in the thalamic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events. Brain Res. Parent A. Matsui M. Surmeier J. et al. Inwardly rectifying potassium (IRK) currents are correlated with IRK subunit expression in rat nucleus accumbens medium spiny neurons. Cooper AJ. The organization of the projection from the cerebral cortex to the striatum in the rat. Neurosci. D2 dopamine receptor-mediated modulation of voltage-dependent Na+ channels reduces autonomous activity in striatal cholinergic interneurons. Griffiths MR. Manabe T. 23:185–215 Nisenbaum ES. Neurophysiol. Exp. J. Neurosci. 2004. 1988. Uchigashima M. 2003. Hernandez-Lopez S. Wilson CJ. Comp. Biamonte F. Neuroscience 29:503–37 Mermelstein PG.annualreviews. Kimura M. Downloaded from www. 1972. Fibers from the basolateral nucleus of the amygdala selectively innervate striosomes in the caudate nucleus of the cat. Faull RL. Brain Res. Prog. Gonon F. . Graybiel AM. 238:286–307 Piomelli D. Surmeier DJ. Hernandez-Lopez S. J. Inhibitory action of dopamine involves a subthreshold Cs(+)-sensitive conductance in neostriatal neurons. Charpier S. Rev. Neurosci.org by University of Manchester . Rev. Neurosci. Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons. J. Malenka RC. Rev. 85:960–76 Maurice N. Fukaya M. J. 4:873–84 Prensa L. Eur. 1998. Mermelstein PG. Nevet A. Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons. 208:259–66 Ragsdale CW Jr. 2001. The selective vulnerability of striatopallidal neurons. Neurosci. J.32:127-147. 2005. Neurol. Nat. 2004. 20:91–127 Parthasarathy HB. 2000. Graybiel AM. Seiger A. Held J. 25:3857–69 Marrone MC. Psychopharmacology (Berl. Arkadir D. 1995. J. 1996. Neuron 43:133–43 Narushima M.John Rylands Library on 10/28/11. Neurol. Yan Z. I. Brain Res. 1989. Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum. The nigrostriatal pathway in the rat: a single-axon study of the relationship between dorsal and ventral tier nigral neurons and the striosome/matrix striatal compartments. 24:2061–70 Matsumoto N. J. Vaadia E. 18:6650–61 Mitchell IJ. 1985. Feedforward inhibition of projection neurons by fastspiking GABA interneurons in the rat striatum in vivo. Rev. Neurosci. 1995. Isolation and characterization of a persistent potassium current in neostriatal neurons. Immunocytochemical localization of choline acetyltransferase within the rat neostriatum: a correlated light and electron microscopic study of cholinergic neurons and synapses. 2009. 24:10289–301 McGeorge AJ. Neurophysiol. Graybiel AM. Wilson CJ. 2007. Cortically driven immediate-early gene expression reflects modular influence of sensorimotor cortex on identified striatal neurons in the squirrel monkey. The cortico-basal ganglia-thalamocortical loop. Keller F. The molecular logic of endocannabinoid signalling. 59:691–719 Morris G.

Neuroscience 86:353–87 Smith Y. USA 89:10178–82 Surmeier DJ. Nathanson NM. Annu. J. Day M. Dopamine D1 receptor modulates the voltage-gated sodium current in rat striatal neurones through a protein kinase A. Eberwine J. Multiple dopamine functions at different time courses. USA 85:5733–37 Richfield EK. J. J. Differential loss of striatal projection neurons in Huntington disease. 1992. Sci. Comp. Physiol. . Comp. J. Shen W. Brain Res. Trends Neurosci. J. Hamilton SE. 16:6579–91 Surmeier DJ. intrinsic organization and co-localization with somatostatin. 1995. 2004. Neurosci. Sadikot AF. Two types of A-current differing in voltage-dependence are expressed by neurons of the rat neostriatum. 103:331–37 Surmeier DJ. 2004. Vanderhaeghen JJ. 2009. Molecular phenotype of rat striatal neurons expressing the dopamine D5 receptor subtype. Rev. Hanley JJ. Surmeier DJ.annualreviews. Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system. Parent A. J. 1989. J. Presynaptic nicotinic cholinergic receptors labeled by [3H]acetylcholine on catecholamine and serotonin axons in brain. 1):95–107 Schultz W. Moratalla R. Cholinergic suppression of KCNQ channel currents enhances excitability of striatal medium spiny neurons. Albin RL. et al. Ulrich S. 2007b. 122:41–46 Tepper JM. Wang Z. J. Kitai ST. Neurosci. 10:1458–66 Sidibe M. Comp. 91:1337–49 Shen W.org by University of Manchester . Neurobiol. Shink E. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. 14:685–92 www. Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey. Neurosci. 372:241–52 Stern EA. 1994. Parent A. Surmeier DJ. Neurophysiol. Neurosci. Proc. 16:2049–58 Rymar VV. Rev. Sadikot AF.2-containing K+ channels regulate subthreshold excitability of striatal medium spiny neurons. Martin AB.Ramanathan S. de la Calle A. 483(Pt. Lett. Neurochem. Vincent JD. Bargas J. 1991. Penney JB. 1998. J.org • Striatal Physiology and Pharmacology 145 Annu. 1995. Neurosci. 2007. 1996. Greengard P. 42:1495–98 Shen W. Foehring RC. Song WJ. Luk KC. Bargas J. Parent A. J. Alberti I. Deniau JM. Kellar KJ. Trends Neurosci. Proc. Kv1. Natl. 2004. Tkatch T. Smith Y. Neuropeptide Y-immunoreactive neurons in the striatum of cat and monkey: morphological characteristics. Neurosci. Stefani A.John Rylands Library on 10/28/11. 2007. Bolam JP. Bolam JP. Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Cholinergic modulation of Kir2 channels selectively elevates dendritic excitability in striatopallidal neurons. Tkatch T. Wilson CJ. Neurosci. Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. Young AB. 2002. Behavioral dopamine signals. Curr. Jacobs O. Downloaded from www. Cao Y. 2007a. Bolam JP. Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. Nat. Bennett BD. Young AB. 1999. 1991. Stefani A. Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity. 2002. 30:228–35 Surmeier DJ. Acad. Kitai ST. Penney JB. Neurosci. For personal use only. 344:1–19 Smith Y. Neurol. 1988.annualreviews. Neurogenesis and stereological morphometry of calretinin-immunoreactive GABAergic interneurons of the neostriatum. Neurol. Natl. Acad. Hemmings HC Jr. Developmental regulation of a slowly-inactivating potassium conductance in rat neostriatal neurons. Sasseville R. Bevan MD. 469:325–39 Sadikot AF. 30:259–88 Schwartz RD. Wilson CJ. 57:1062–67 Schiffmann SN. Yan Z. 30:203–10 Schultz W. Held JE. D’Amato CJ. Tian X. Eur. Thalamic inputs to striatal interneurons in monkeys: synaptic organization and co-localization of calcium binding proteins. Smith Y. Neuron 14:385–97 Surmeier DJ. Neuroscience 30:767–77 Rivera A. 1992.32:127-147. Nature 394:475–78 Surmeier DJ. Microcircuitry of the direct and indirect pathways of the basal ganglia. Narvaez JA. 1986. Ding J. Neuroscience 89:1189–208 Smith Y. Nairn AC. 320:228–42 Schiffmann SN. Hernandez-Lopez S. 25:7449–58 Shen W. Jaeger D. Functional diversity and specificity of neostriatal interneurons. Dopamine receptor subtypes colocalize in rat striatonigral neurons. 1989. Bolam JP. 1984. 1998. Bolam JP. Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic interneurons in the rat striatum. Membrane potential synchrony of simultaneously recorded striatal spiny neurons in vivo. 22:8158–69 Reiner A. Anderson KD. Neurosci. 2005. Sci. Kitai ST. Lledo PM. Neurochem. Lehmann J. Lett. Day M. Neurol. Opin. J.

16:2592– 604 Yan Z. Neurosci. J. 2006. J. G-protein pathway. Acad. D2 dopamine receptors reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited. 10:508–19 Wilson CJ. Double anterograde tracing of outputs from adjacent “barrel columns” of rat somatosensory cortex. Brain Res. monkey and human. USA 103:8251–56 Yoshida M. Salin P. Kawaguchi Y. Fujimoto K. 2000. Knowlton BJ. J. North RA. Neurol. Surmeier DJ. Comp. Koos T. Pharmacol. For personal use only. 2006.Tepper JM. Elde RP. et al. 1990. Proc. 20:579–88 Uchimura N. J. protein-kinase-C-insensitive pathway. Niijima K. Kitai ST. 1991.annualreviews. 1996. 863:182–91 Yamada H. Parent A.2 mRNA abundance and A-type K(+) current amplitude are linearly related in basal ganglia and basal forebrain neurons. Levey AI. Br. 2000. Hutton EA. Res. Ingham CA. Lovinger DM. 62:1280–86 Uchimura N. 2006. USA 87:7050–54 Wilson CJ. . J. GABAergic microcircuits in the neostriatum.and P-type Ca2+ currents in rat neostriatal cholinergic interneurons through a fast. 1997. 220:67–80 Wilson CJ. 477:241–51 Wang Z. Flores-Hernandez J. Natl. Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling. Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia. Neurosci. Nieoullon A. The generation of natural firing patterns in neostriatal neurons. Surmeier DJ. et al. Neurosci. 10:34–51 146 Kreitzer Annu.John Rylands Library on 10/28/11. Chang HT. Arbuthnott GW. Neurosci. Neurophysiol. 1989. Rev. Groves PM.32:127-147. Johansson O. Smith Y. J. 7:464–76 Yin HH. parvalbumin or NADPH-diaphorase: a comparative study in the rat. Neuron 45:575–85 Wilson CJ. Muscarinic (m2/m4) receptors reduce N. 2000. 2006. Ultrastructural features of NPY-containing neurons in the rat striatum. 1990. Neuronal mechanism underlying dystonia induced by bicuculline injection into the putamen of the cat. Song WJ. Trends Neurosci. 99:736–40 Vincent SR. The role of the basal ganglia in habit formation. North RA. 2009. Brain Res. Kai L. Neuron 50:443–52 Weiner DM. J. Firing patterns and synaptic potentials of identified giant aspiny interneurons in the rat neostriatum. Rev. Inward rectification in rat nucleus accumbens neurons. 95:196–204 Wilson CJ. Baranauskas G. Proc. Striatal interneurons expressing calretinin. Sci. Natl. Hokfelt T. Brain Res. J. 16:2397–410 Wright AK. 217:252–63 Vuillet J. Day M. 27:662–69 Thomas TM. Actions of cocaine on rat nucleus accumbens neurones in vitro. NADPH-diaphorase: a selective histochemical marker for striatal neurons containing both somatostatin. 2001. 1993. Prog. Hersch SM. Nagatsuka Y. Yoshida M. Neurosci. Neuron 19:1115–26 Yin HH. Kv4. 1995. Neurophysiol. 1983. 77:1003–15 Yan Z. J. Downloaded from www. 1999. Acad. Wilson CJ. 1990. 1996. Skirboll L. Cherubini E. Origin of the slow afterhyperpolarization and slow rhythmic bursting in striatal cholinergic interneurons. D5 dopamine receptors enhance Zn2+ -sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Cortical inputs to m2-immunoreactive striatal interneurons in rat and monkey. The mechanism of intrinsic amplification of hyperpolarizations and spontaneous bursting in striatal cholinergic interneurons. 99:277–97 Wilson CJ. Kerkerian L. Levey AI. Brain Res.org by University of Manchester . Sci. Neurosci. Neurophysiol. Surmeier DJ. The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons. Neuroscience 103:1017–24 Yan Z.and avian pancreatic polypeptide (APP)-like immunoreactivities. Brann MR. Synapse 37:252–61 Tkatch T. Surmeier DJ. Surmeier J. Brain. Nat. Neurosci. Yin HH. 1989. Ronesi J. 2005. membrane-delimited. Coordinated expression of muscarinic receptor messenger RNAs in striatal medium spiny neurons. Neostriatal projection patterns and terminal ultrastructure. 2004. Norrie L. Res. Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Spontaneous firing patterns of identified spiny neurons in the rat neostriatum. Muramatsu S. 1997. Neuroscience 88:119–33 Wu Y. 1981. Differential roles of the caudate nucleus and putamen in motor behavior of the cat as investigated by local injection of GABA antagonists. Goldberg JA. 677:333–36 Yan Z.

32:127-147. An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Rev. 1995. Neurosci. For personal use only. Neurobiol.annualreviews. 2009. Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy. Levey AI. 2002. 2000. Neurosci. 24:85–105 Zhou FM. Rev. Bolam JP.John Rylands Library on 10/28/11. Downloaded from www.org by University of Manchester . Biobehav. Smith AD. Neuroscience 65:709–30 Zahm DS. Cholinergic interneuron characteristics and nicotinic properties in the striatum. 53:590–605 Annu. Wilson CJ. J.Yung KK. www.org • Striatal Physiology and Pharmacology 147 .annualreviews. Ciliax BJ. Hersch SM. Dani JA.

org by University of Manchester . 2009.S. Donoghue p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 249 The Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation T.annualreviews. Huys p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p95 Physiology and Pharmacology of Striatal Neurons Anatol C. Robbins and A. Arnsten p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 267 v .F. Joachim Scholz.John Rylands Library on 10/28/11.T.M. Woolf p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 1 Synaptic Mechanisms for Plasticity in Neocortex Daniel E.W. Hatsopoulos and John P. Rushworth p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p75 Serotonin in Affective Control Peter Dayan and Quentin J. Hariri p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 225 The Science of Neural Interface Systems Nicholas G.32:127-147. Volume 32. and Clifford J. 2009 Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage Michael Costigan. and Barbara J. Rev. Sahakian p p p p p p p p p p p p p p p p p p p p p p p p p p57 Using Diffusion Imaging to Study Human Connectional Anatomy Heidi Johansen-Berg and Matthew F. Downloaded from www. Feldman p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p33 Neurocognitive Mechanisms in Depression: Implications for Treatment Luke Clark. Samuel R. For personal use only. Chamberlain. Kreitzer p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 127 The Glial Nature of Embryonic and Adult Neural Stem Cells Arnold Kriegstein and Arturo Alvarez-Buylla p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 149 Representation of Number in the Brain Andreas Nieder and Stanislas Dehaene p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 185 Neuronal Gamma-Band Synchronization as a Fundamental Process in Cortical Computation Pascal Fries p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 209 The Neurobiology of Individual Differences in Complex Behavioral Traits Ahmad R. Neurosci.Annual Review of Neuroscience Contents Annu.

Fiez p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 413 Advances in Light Microscopy for Neuroscience Brian A. Bashaw p p p p p p p p p p p p p p p p p p p p p p p p p p p p 383 Cerebellum and Nonmotor Function Peter L. Rev. Laurie D. Averbeck p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 315 Establishment of Axon-Dendrite Polarity in Developing Neurons Anthony P. Richard P. Wilt. Mukamel. Neurosci. and Julie A. For personal use only. Kunal K. Ghosh. Schnitzer p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 435 Indexes Cumulative Index of Contributing Authors. Rodrigues. and Robert M. Rebecca K. Burns. Dum. and Greg J.The Influence of Stress Hormones on Fear Circuitry Sarina M. Eric Tatt Wei Ho. Romanski and Bruno B.org by University of Manchester . LeDoux. Downloaded from www. Volumes 23–32 p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 511 Errata An online log of corrections to Annual Review of Neuroscience articles may be found at http://neuro. Joseph E. Volumes 23–32 p p p p p p p p p p p p p p p p p p p p p p p p p p p 507 Cumulative Index of Chapter Titles. Barnes and Franck Polleux p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p p 347 Axon Growth and Guidance: Receptor Regulation and Signal Transduction Michael O’Donnell.annualreviews. Chance. and Mark J.annualreviews. Eran A. Strick.32:127-147. vi Contents . 2009.org/ Annu.John Rylands Library on 10/28/11. Sapolsky p p p p p p p p p p p p p p p p p p p p p p p 289 The Primate Cortical Auditory System and Neural Representation of Conspecific Vocalizations Lizabeth M.