Synaptic Transmission

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Synaptic Transmission
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Otto Loewi

• 1920 - showed communication at gap between nerve
  heart muscle was chemical
• 1936 - Nobel Prize

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Loewis Experiment

• Stimulate Vagus Nerve - slows heart. Transfer
  fluid, 2nd heart slows
• Stimulate another nerve speed up rate
• CONCLUSION
• Chemical communication
• Different chemicals released from different
  nerves, have different effects

Fig 5.2
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Chemical Signaling at Synapses
Postsynaptic Neuron
Presynaptic Neuron
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Anatomy of a Synapse
Synaptic Vesicle
Presynaptic Terminal
Enzymes
Synaptic Cleft
Receptors
Postsynaptic Neuron
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(No Transcript)
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Sequence of Events at the Synapse
EXCOCYTOSIS
1) synthesis
2) release
4) inactivation
3) receptor activation
Fig 5.5
Fig 5.6
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4 Ways to Remove Neurotransmitter
REUPTAKE
DEGRADATION

• Degradation via enzymes in cleft
• Re-uptake via transporter protein
• Glial cell uptake
• Diffusion away from cleft

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Synaptic Transmission
Ion flow ? EPSP or IPSP
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Agonists Antagonists
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Types of Synapses
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Ionotropic Receptors
Fig 5.15
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Metabotropic Receptors
Fig 5.16
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Neurotransmitters
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• Acetylcholine (ACh)
• Monoamines
• Norepinephrine (NE)
• Dopamine (DA)
• Serotonin (5-HT)
• Soluble gases
• Nitric oxide
• CO
• Amino Acids
• GABA
• Glutamate
• Opioid peptides

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ACh

• 1st discovered
• Wide distribution in CNS PNS
• Can be excitatory or inhibitory
• Functionally involved in a variety of behaviors
  including emotions, memory

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Cholinergic Pathways Ascending projections to
many brain regions
Note - cell bodies clustered in a few nuclei
in/near brainstem, but axons are widely
distributed in forebrain, brainstem SC.
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ACh Synthesis
vege's egg yolk kidneys liver legumes
Acetyl CoA (mitochondria) Choline (diet)
Choline Acetyltransferase (ChAT)
ACh
AChE (acetylcholinesterase) breaks ACh down in
cleft, Products taken back up in cell.
1 AChE can breakdown 14,000 ACh molecules/sec!
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ACh Receptors

• All ACh receptors respond to ACh
• NICOTINIC (NM junction ANS)
• 8 subtypes
• stimulated by nicotine, antagonized by curare
• MUSCARINIC (CNS)
• 5 subtypes
• stimd by muscarine, antagonized by scopolamine
  atropine (used to dilate eyes)

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Neuromuscular Junction
Nicotinic receptors - stop Ach activity stop
muscle activity including diaphragm
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WHAT HAPPENS IF YOU BLOCK ACh Activity?!
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Direct Antagonist

• Atropine - muscarinic receptor blocker
• Dilates eyes
• In brain hallucinations

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Curare
Antagonist at Cholinergic Receptors on Muscles in
PNS
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Botulinum Toxin - indirect antagonist
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Blocks ACh release 1 gram enough to kill 350,000
people
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Black Widow Spider Venom
Massive exocytosis followed by vesicle
depletion no more neurotransmission
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AChE Inhibitors

• Antidote for curare - competes w/ curare
  molecules
• Nerve gases - affects CNS PNS
• Sweating, bronchia fill w/ mucus constrict,
  dimmed vision, vomiting, convulsions, paralysis
  asphyxiation

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MONOAMINES (aka bioamines)

• Nuclei located in brainstem and project
  throughout brain
• Modulate function of widespread regions of the
  brain

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DOPAMINE (DA)

• 3 Important DA
• Projections
• Nigrostriatal
• Mesolimbic
• Mesocotical

Antagonists - antipsychotics Agonists -
recreational drugs Parkinsons Disease
VTA
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Central Vigilance, sleep, limbic hypothalamic
activities
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Behavioral Functions

• Food intake (satiety) -
• Obsessive-Compulsive Disorder - 5-HT agonists
  improve
• Mood
• Sleep/arousal

Only about200,000 cells, but fibers thruout the
brain
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Amino Acid NTs GABA Glutamate

• most common NTs
• Found throughout CNS at high concentrations
• Several Receptors
• Inactivation Reuptake into terminal Glial cell

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Neuropeptides

• Made in soma transported (SLOW PROCESS not
  replaced quickly)
• Opioid Peptides (endorphins enkephalins)
• Receptors - several subtypes
• Inactivation - Peptidase (NO RE-UPTAKE)

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Transmitter Gases Nitric oxide (NO) Carbon
monoxide (CO)

• Not stored or vesicular release
• Synthd as needed
• Produced in all regions of neuron