Transcript Synaptic Transmission Lecture

Neuronal
Transmission
BN Fall 2011
Julia Sobesky
• Types of synapses
• Electrical
• Chemical
Outline
• Neurotransmitters
•
•
•
•
Criteria
Types
Release
Inactivation
• Receptor types
• Ionotropic
• Metabotropic
• Ligand binding
• Plasticity
Electrical synapse:
gap junctions
• ~3nm apart
• Very fast communication
• Direct pore between cells,
allows bidirectional flow of
ions
• 6 connexins= 1 connexon
• Allows rapid and synchronous
firing of interconnected cells
Why would we need
anything more?
• Why don’t our brains just use electrical transmission?
Benefits of Chemical
signaling
• 60+ different NTs and neuromodulators
• Each NT can have up to 15 different receptors
• Co-localization of several NTs in one synapse
• One neuron can have TONS of different
synapses
• Simple or complex post-synaptic responses
The chemical synapse
• ~20-50 nm apart
• NTs released by presynaptic cell bind receptors
on post-synaptic membrane
• EPSP, IPSP or complex
responses
• *** The RECEPTOR
determines the response,
not the NT ***
Criteria for NTs
• Synthesized in presynaptic cell
• Activity dependent
release
• Mechanism for
deactivation
• Predictable
pharmacological
activity
Major classes of
neurotransmitters
• Small neurotransmitter molecules
• Synthesized near axon terminals
• Acetylcholine, monoamines, indolamines, amino
acids
• Large neurotransmitter moleculesNeuropeptides
• Synthesized in soma
• hormones
• enkephalin/ endorphin
• Soluble gasses
• nitric oxide
• carbon monoxide
Small Neurotransmitters
• 1. Amino Acids
• Glutamate/ Gamma-aminobutyric acid (GABA)
• MAJOR NTs in the CNS/ All over
• 2. The Monoamines
• Catecholamines
• Dopamine- DA- reward/movement
• Norepinephrine- NE –sympathetic
• Epinephrine-released from adrenals
• Indolamines
• Serotonin -5-HT
• 3. Acetylcholine (ACh)
Amino Acids
Catecholamines
Glutamate
Tyrosine
Tyrosine
Hydroxylase
Glutamic
Acid
Decarboxylase
(GAD)
L-Dihydroxyphenylalanin
(L-Dopa)
GABA
Dopamine
Norepinephrine
Epinephrine
Then what?
• NTs are synthesized at terminal and packaged
• Or
• Neuropeptides are transcribed, translated,
packaged and trafficked down to the terminal
• How does an Action Potential initiate their
release?
Exocytosis
Ca++ facilitated
SNARE Proteins
What happens to NTs
after release?
• Diffusion through synapse to post-synaptic cell
• NT binding to receptors is TRANSITORY, more
NT around to bind, the greater the receptor
effects
• …….
2 Main Types of
Receptors
Ionotropic
• Ligand-gated ion
channels
• Directly alters the
membrane potential
Metabotropic
• Slower, but can have
greater effects
• 2 types:
• G-protein coupled
• Tyrosine Kinase
receptors
Ionotropic Receptors
• Excitatory (EPSP) or
Inhibitory (IPSP)
responses
• K+, Na+, Ca++
• CL• Some can be ligand
and voltage-gated
(NMDA)
Complex effects of
metabotropic receptors
• NO PORE, but binding can
initiate:
• 2nd messenger system
• Other products could open
ion channels
• Modulate enzyme activity
• Regulate ion channels in
membrane
• Initiate gene
transcription/translation
What happens to NTs
after release?
• Diffusion through synapse to post-synaptic cell
• NT binding to receptors is TRANSITORY, more
NT around to bind, the greater the receptor
effects
• NT must be cleared
• removal just as important as release
• Multiple things can happen….
Uptake and degradation
Glial Sponge
• Glial cells can act as
buffers for excess NTs
• Can process and
release NTs
• Passive diffusion away
from the synapse
• Why?
NT binding to receptor
shape-specific
• Lock and key arrangement
• Agonists
• Endogenous vs. exogenous
• Antagonists
• Drugs work because we
already have the receptors
in place to receive them
• Full vs. partial
• Drug actions are so intense
because they cause actions
so far above and beyond
what endogenous
compounds do
• Competitive vs. noncompetitive
• Allosteric
Receptor agonists and
antagonists
Organization dictated by
experience
• Synapses can grow and
retract, continually
being altered by use
• Plasticity can occur in a
variety of ways:
• Create new synapses
• Strengthen or weaken
existing synapses
• Break old connections
Synaptic connections
change over time
Putting it all together:
Neuropharmacology
• Tolerance develops due
to cellular and receptor
alterations in response
to chronic drug use
• The changes also
mediate withdrawal
symptoms
• Withdrawal= opposite
of drug effects
• Depression is most
likely not due to a lack
of serotonin (i.e. SSRIs)
• …Serotonin receptor is
metabotropic
• Severe alcohol
withdrawal can kill you:
• Seizures
• Glutamate
excitotoxicity
Organization dictated by
experience
Thanks! Questions?