Lecture 5: Neurotransmission II

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Psy 111 Basic concepts in Biopsychology Lecture
5 Neurotransmitter Systems
Website http//mentor.lscf.ucsb.edu/course/summer
/psyc111/
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Objectives

• Identify the criteria for molecules to serve as a
  neurotransmitter discuss types of molecules
  that fulfull these criteria and techniques to
  study them.
• Describe the variability in synaptic morphology
  and function.
• Survey the major classes of neurotransmitters
  amino acids, amines, peptides.
• Provide a framework for consideration of levels
  of neurotransmission
• Discuss glutamate as the major excitatory NT
• Discuss GABA as the major inhibitory NT
• Discuss the amines and general function
• Describe neuropeptides
• Discuss retrograde transmission.

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Neurotransmitter Systems

• Criteria for neurotransmitters
• Synthesized and stored in presynatpic neuron
• Released from presynatpic neuron on stimulation
• Exogenous application mimics endogenous action

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Types of Neurotransmitters
Amino Acids
Amines
Peptides
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Synapse variability

• Immense variability in synapses in the brain and
  spinal cord
• Site of synapse on target cell
• Size of synapse
• Structures of synapse
• Chemical transmitter

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CNS Synapses Configurations
Axosomatic
Axodendritic
Axoaxonic
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Types Chemical Synapses Neuromuscular Junction

• large synapse
• postsynaptic cell has 1 input
• strong/reliable
• Presynaptic neuron AP always produce postsynaptic
  muscle response.

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Types Chemical Synapses CNS Synapse

• small synapse
• many inputs per cells
• Weak

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Comparison of Neuromuscular Junction (NMJ) and
CNS Synapses
Property of Synapses NMJ CNS   Inputs
1 100's - 1000's   Size large small   St
rength strong (70 mV) weak (1mV)   Neurotran
smitter always ACh many   Type of
Response excitatory excitatory,
inhibitory, modulatory Receptor
Type ion channel ion channel,
metabotropic
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CNS Synapses Postsynaptic size
Grays Type II -Inhibitory
Grays Type I -Excitatory
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Diffuse Modulatory System
loose synapse

• Characteristics
• Core of neurons
• Core in brain stem
• Loose Synapse
• Metabotropic receptors

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(oversimplified) Hierarchy of chemical control
Projection Local Diffuse modulatory
Soma dendrites
Axon
Projection Neuron
Diffuse Neurons
Local Neuron
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Survery of Neurotransmitters

• Amino acids fast signaling
• Amines (incl. acetylcholine) slow signaling
• Neuropeptides
• (Retrograde signaling).

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Types of Neurotransmitters
Amino Acids
Amino Acids modified and packaged in
terminal Amines synthesized and packaged in
terminal Peptides synthesized in soma (rER)
and transport to terminal
Amines
Peptides
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Glutamate (amino acid)
-present in all cells
All cells have this protein since needed for
protein synthesis.
Use this protein to identify glutamate-releasing
(aka glutamatergic) neurons
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Glutamate Receptors
major excitatory NT in Brain -3 channel-coupled
all produce EPSPs (depolarize) -8 G-protein
coupled (mGluR1-8) - either Gi or Gq (excitatory)
or Go
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NMDA Receptor
NMDA Receptor -transmitter-gated -voltage-gated
depoln removes Mg -important for
neuroplasticity

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GABA (Gama-amino butyric acid)
major inhibitory NT in Brain -synthesized from
glutamate by GAD (glutamate decarboxylase) -GABA
transporter on vesicles.
Use these protein to identify GABA-releasing (aka
GABAergic) neurons
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GABA (Gama-amino butyric acid)
major inhibitory NT in Brain -1 channel-coupled
- GABAA Receptor Cl- channel (IPSP or block
EPSP) -2 G-protein coupled GABAB1-2 Receptors
inc IK or dec ICa
These drugs have different sites of action on the
same channel effect synergizes therefore dont
mix or you will die!
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Steroid Modulation of NT Receptors
Progesterone increases hyperpolization via GABAA
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Steroid (progestins) Modulation of GABAA
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Acetylcholine

• synthesized by choline acetyltransferase (ChAT).
• degraded by acetylcholine esterase (AChE).
• -1 channel coupled nicotinic depolarization
• -5 G-Protein muscarinic - Gi or Gs or Go
• Transmission terminated by Ach breakdown by AChE.
• Diffuse Modulatory System.

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Acetylcholine
Basal forebrain cells have very diffuse
projections Basal forebrain -learning/memory Midb
rain -regulate sensory systems
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Catecholamines
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Dopamine
-synthesized by Dopa decarboxylase -degraded by
monoamine oxidase -5 G-Proteins- D1- D5 D1, D5
Gs (activates cAMP pathway) D2, D3, D4 Gi
(inhibits cAMP pathway) (no channel-coupled
receptors i.e. no fast neurotransmission) Transm
ission terminated by reuptake via dopamine
transporters (DAT) degradation
(MAO). Autoreceptors (D2R) play important role
in control of release. -diffuse modulatory system
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Dopamine
SN motor VTA - motivation
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Dopamine target of drugs of abuse
VTA
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Norepinephrine (noradrenalin)
-synthesized by dopamine B-hydroxylase -degraded
by monoamine oxidase (MAO) -4 G-Proteins-
alpha1-2, beta 1-2 alpha Gi beta Gs (no
channel-coupled receptors i.e. no fast
neurotransmission) -Epinephrine (adrenalin)
binds to same receptors-acts as
hormone Transmission terminated by reuptake via
NE transporters (NET) degradation
(MAO). -diffuse modulatory system
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Norepinephrine
Arousal functions -attention, learning,
sleep/wake, anxiety, etc
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Serotonin
-synthesized from Tryptophan (2 steps) -degraded
by monoamine oxidase -23 Receptors 5
subtypes 5-HT1, 5HT2,5-HT5 5-HT3 channel
coupled Rest G-Protein coupled Transmission
terminated by reuptake via 5HT transporters
(SERT) degradation (MAO). -diffuse modulatory
system
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Serotonin
Many nuclei in Raphe Arousal functions -mood,
sleep/wake
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Serotonin antidepressants
New antidepressants block 5HT transporter
SSRI -inc only 5HT
Old antidepressants inhibit MAO (MAOI) -inc
5HT, NE, DA.
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Peptide Neurotransmitters
-Made as polypeptides synthesized on rER,
packaged by Golgi apparatus, transported on
microtubles -HUGE diversity of peptides serve as
transmitters -co-localized with amino acid or
amine NTs -Release in response to prolonged
stimulation -all receptors appear to be G-Protein
coupled
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Co-localization of Neurotransmitters
Peptides are found in same neuron as amino acid
or amine transmitters. But are released only
after prolonged activation (mechanism unknown).
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Retrograde signaling Diffusible Gases (nitric
oxide)

• diffusible gases Nitric oxide (NO) carbon
  monoxide (CO).
• enzymatically synthesized in neurons.
• no active release i.e. diffuse from source.
• appears to constitute retrograde communication
  system (i.e. postsynaptic to presynaptic)

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Retrograde signaling Endocannabinoids

• Post to Pre synaptic neurons.
• Elevated Ca in postsynaptic cell activates
  synthetic enzymes.
• Enzymes synthesize endocannabinoid
• Release is automatic membrane permeable, not
  stored in vesicles.
• Bind to CB1 receptors.

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Studying Neurotransmitter Systems

• Criteria for neurotransmitters
• Synthesized and stored in presynatpic neuron
• Released from presynatpic neuron on stimulation
• Exogenous application mimics endogenous action

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Studying NT Systems Detecting the suspected NT
in neurons
In situ hybridization to detect mRNA localize
RNA to cell body.
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Studying NT Systems Detecting the suspected NT
in neurons
Immunocytochemistry to detect specific proteins
can be peptide neurotransmitter, synthetic
proteins, or vesicular transporters.
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Exogenous stimulation

• Microionophoresis Application of substance
  causes response.
• Response is similar to stimulation of axon.