NEUROTRANSMITTER SYSTEMS

NEUROTRANSMITTER
Basic criteria: 1. The molecule must be synthetized and stored in the presynaptic neuron 2. The molecule must be released by the presynaptic axon terminal upon stimulation 3. The molecule, when experimentally applied, must produce a response in the postsynaptic cell that mimics the response generated by the release of the neurotransmitter by the presynaptic cell

HOW TO STUDY NEUROTRASMITTERS

Localization of Transmitters and Transmitter-synthesizing enzyme Immunocytochemistry Anatomically localize particular molecules to particular cells

HOW TO STUDY NEUROTRASMITTERS

Studying Transmitter Localization In situ hybridization mRNA strands can be detected by complementary probe Probe can be radioactively labeled - autoradiography

HOW TO STUDY NEUROTRASMITTERS

Studying Transmitter Release

Loewi and Dale identified Ach as a transmitter CNS contains a diverse mixture of synapses that use different neurotransmitters impossible to stimulate a single population of synapses Brain slice as a model (ex vivo, brain in a dish) Kept alive in vitro Stimulate synapses, collect and measure released chemicals (mixture) Often stimulated by high K+ solution to cause massive synaptic release Ca2+ dependency of the release has to be confirmed

HOW TO STUDY NEUROTRASMITTERS

Studying Receptors No two transmitters bind to the same receptor; however one neurotransmitter can bind to many different receptors
Receptor subtypes Neuropharmacology Subtype specific agonists and antagonists ACh receptors

Skeletal muscle

Heart

HOW TO STUDY NEUROTRASMITTERS

Studying Receptors

HOW TO STUDY NEUROTRASMITTERS

Studying Receptors
Ligand-binding methods Drugs that interact selectively with neurotransmitter receptors were used to analyze natural receptors Solomon Snyder and opiates Identified receptors in brain Subsequently found endogenous opiates Endorphins, dynorphins, enkephalins Enormously important for mapping the anatomical distribution of different neurotransmitter receptors in brain

NEUROTRASMITTER CHEMISTRY
Cholinergic (ACh) Neurons good marker for cholinergic neurons

Rate-limiting step of Ach synthesis

Secreted from the axon terminal and associated with axon terminal membrane

NEUROTRASMITTER CHEMISTRY
Cholinergic (ACh) Neurons Synthesis

Degradation

NEUROTRASMITTER CHEMISTRY
Catecholaminergic Neurons Involved in movement, mood, attention, and visceral function
Tyrosine: Precursor for three amine neurotransmitters that contain catechol group Dopamine (DA) Norepinephrine (NE, noradrenaline) Epinephrine (E, adrenaline)

NEUROTRASMITTER CHEMISTRY
Marker for catecholaminergic neurons
Rate limiting, regulated by physiological signals
Low-rate release - increased catecholamine conc. - inhibit TH activity High-rate release - increased Ca2+ influx - boost TH activity

Present in the synaptic vesicles

Present in the cytosol Released from the adrenal gland as well

NEUROTRASMITTER CHEMISTRY
Serotonergic Neurons
Serotonin (5-HT,5hydroxytryptamine) is derived from tryptophan Regulates mood, emotional behavior, sleep Synthesis of serotonin
Limited by the availability of blood tryptophan (diet)
Selective serotonin reuptake inhibitors (SSRIs):

Antidepressants

NEUROTRASMITTER CHEMISTRY
Amino Acidergic Neurons Amino acid neurotransmitters: Glutamate, glycine, gammaaminobutyric acid (GABA) Glutamate and glycine
Present in all cells - Differences among neurons are quantitative NOT qualitative Vesicular transporters are specific to these neurons

Glutamic acid decarboxylase (GAD)

Key enzyme in GABA synthesis Good marker for GABAergic neurons One chemical step difference between major excitatory transmitter and major inhibitory transmitter