Neurotransmitters

Copyright 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins
Neuroscience: Exploring the Brain, 3e

Chapter 6: Neurotransmitter Systems
Introduction
Three classes of neurotransmitters
Amino acids, amines, and peptides
Many different neurotransmitters
Defining particular transmitter systems
By the molecule, synthetic machinery, packaging,
reuptake and degradation, etc.
Acetylcholine (Ach)
First identified neurotransmitter
Nomenclature (-ergic)
Cholinergic and noradrenergic
Studying Neurotransmitter Systems
Neurotransmitter - three criteria
Synthesis and storage in presynaptic neuron
Released by presynaptic axon terminal
Produces response in postsynaptic cell
Mimics response produced by release of
neurotransmitter from the presynaptic neuron
Studying Transmitter Localization
Transmitters and Transmitter-Synthesizing Enzymes
Immunocytochemistry localize molecules to
cells
Studying Transmitter Localization (Contd)
In situ hybridization
Localize synthesis of protein or peptide to a cell
(detect mRNA)
Studying Transmitter Release
Transmitter candidate: Synthesized and
localized in terminal and released upon
stimulation
CNS contains a diverse mixture of synapses that
use different neurotransmitters
Brain slice as a model
Kept alive in vitro Stimulate synapses,
collect and measure released chemicals
Studying Synaptic Mimicry
Qualifying condition: Molecules evoking same response as
neurotransmitters
Microionophoresis: Assess the
postsynaptic actions
Microelectrode: Measures effects on
membrane potential
Studying Receptor Subtypes
Neuropharmacology
Agonists and antagonists
e.g., ACh receptors
Nicotinic, Muscarinic
Glutamate receptors
AMPA, NMDA, and
kainite
Studying Receptors (Contd)
Ligand-binding methods
Identify natural receptors using radioactive ligands
Can be: Agonist, antagonist, or chemical
neurotransmitter

Studying Receptors (Contd)
Molecular analysis- receptor protein classes
Transmitter-gated ion channels
GABA receptors
5 subunits, each made with 6 different
subunit polypeptides
G-protein-coupled receptors
Neurotransmitter Chemistry
Evolution of neurotransmitters
Neurotransmitter molecules
Amino acids, amines, and peptides
Dales Principle
One neuron, one neurotransmitter
Co-transmitters
Two or more transmitters released from one nerve
terminal
An amino acid or amine plus a peptide
Cholinergic (ACh) Neurons
Cholinergic (ACh) Neurons
Catecholaminergic Neurons
Involved in movement, mood, attention,
and visceral function
Tyrosine: Precursor for three amine
neurotransmitters that contain catechol
group
Dopamine (DA)
Norepinephrine (NE)
Epinephrine (E, adrenaline)
Serotonergic (5-HT) Neurons
Amine neurotransmitter
Derived from tryptophan
Regulates mood, emotional behavior, sleep
Selective serotonin reuptake inhibitors (SSRIs) -
Antidepressants
Synthesis of serotonin
Amino Acidergic Neurons
Amino acidergic neurons have amino acid
transporters for loading synaptic vesicles.
Glutamic acid decarboxylase (GAD)
Key enzyme in GABA synthesis
Good marker for GABAergic neurons
GABAergic neurons are major of synaptic
inhibition in the CNS
Other Neurotransmitter
Candidates and Intercellular
Messengers
ATP: Excites neurons;
Binds to purinergic
receptors
Endocannabinoids
Retrograde messengers
Transmitter-Gated Channels
Ionotropic receptors
Introduction
Fast synaptic transmission
Sensitive detectors of chemicals and voltage
Regulate flow of large currents
Differentiate between similar ions


The Basic Structure of Transmitter-Gated Channels
Pentamer: Five protein subunits

Amino Acid-Gated Channels
Glutamate-Gated Channels
AMPA, NMDA, kainite
Voltage dependent NMDA
channels
GABA-Gated and Glycine-Gated Channels
GABA mediates inhibitory transmission
Glycine mediates non-GABA inhibitory transmission
Bind ethanol, benzodiazepines, barbiturates
G-Protein-Coupled Receptors and
Effectors
Three steps
Binding of the neurotransmitter to the receptor
protein
Activation of G-proteins
Activation of effector systems
The Basic Structure of G-Protein-Coupled Receptors
(GPCRs)
Single polypeptide with seven membrane-spanning
alpha-helices
Effectors
The Ubiquitous G-Proteins
GTP-binding (G-) protein
Signal from receptor to effector proteins

Effectors
The Ubiquitous G-Proteins (Contd)
Five steps in G-protein operation
Inactive: Three subunits -
, and
- float in
membrane (
bound to GDP)
Active: Bumps into activated receptor and
exchanges GDP for GTP
G
-GTP and G
- Influence effector proteins

G
inactivates by slowly converting GTP to GDP

G
recombine with G
-GDP

Effectors
GPCR Effector Systems
The Shortcut Pathway
From receptor to G-protein to ion channel; Fast
and local
Effectors
GPCR Effector Systems
Second Messenger Cascades
G-protein: Couples neurotransmitter with
downstream enzyme activation
Effectors
GPCR Effector Systems (Contd)
Push-pull method (e.g., different G
proteins for stimulating or inhibiting
adenylyl cyclase)
Effectors
Some cascades split
G-protein activates PLC generates
DAG and IP3 activate different
effectors
Effectors
Signal amplification
Effectors
Phosphorylation and Dephosphorylation
Phosphate groups added to or removed from a protein
Changes conformation and biological activity
The Function of Signal Cascades
Signal amplification by GPCRs
Divergence and Convergence
in Neurotransmitter Systems
Divergence
One transmitter activates
more than one receptor
subtype greater
postsynaptic response
Convergence
Different transmitters
converge to affect same
effector system
Concluding Remarks

Neurotransmitters
Transmit information between neurons
Essential link between neurons and effector cells
Signaling pathways
Signaling network within a neuron somewhat
resembles brains neural network
Inputs vary temporally and spatially to increase
and/or decrease drive
Delicately balanced
Signals regulate signals- drugs can shift the
balance of signaling power
End of Presentation

Neurotransmitters

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Copyright 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Neuroscience: Exploring the Brain, 3e

- Influence effector proteins

inactivates by slowly converting GTP to GDP

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