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
Ca
2+
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 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)
Marker for catecholaminergic neurons
Rate limiting, regulated by
physiological signals
Low-rate release - increased
catecholamine conc. - inhibit TH activity
High-rate release - increased Ca
2+
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,5-
hydroxytryptamine) 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, gamma-
aminobutyric 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
NEUROTRASMITTER CHEMISTRY