2020-09-29 08:51:19

Prelude (4:44)

Today’s Topics

  • How neurons talk to one another
  • Synaptic communication

In the beginning

  • Soma receives input from dendrites
  • Axon hillock sums/integrates
  • If sum > threshold, AP “fires”

Illustration of summation

1224 Post Synaptic Potential Summation

Steps in synaptic transmission

  • Rapid change in voltage triggers neurotransmitter (NT) release
  • Voltage-gated calcium Ca++ channels open
  • Ca++ causes synaptic vesicles to bind with presynaptic membrane, merge, exocytosis
  • NTs diffuse across synaptic cleft

Steps in synaptic transmission

  • NTs bind with receptors on postsynaptic membrane
  • Receptors respond
  • NTs unbind, are inactivated

Synaptic transmission

SynapseSchematic en

Exocytosis

Why do NTs move from presynaptic terminal toward postsynaptic cell?

  • Electrostatic force pulls them
  • Force of diffusion

Why do NTs move from presynaptic terminal toward postsynaptic cell?

  • Electrostatic force pulls them
  • Force of diffusion

Postsynaptic receptor types

  • Ionotropic (receptor + ion channel)
    • Ligand-gated
    • Open/close ion channel
    • Ions flow in/out depending on membrane voltage and ion type
    • Faster, but short-acting effects

Postsynaptic receptor types

  • Metabotropic (receptor only, no attached ion channel)
    • Trigger 2nd messengers
    • G-proteins
    • Open/close adjacent channels, change metabolism
    • Slower, but longer-lasting effects

Receptor types

Receptors generate postsynaptic potentials (PSPs)

  • Small voltage changes
  • Amplitude scales with # of receptors activated
  • Excitatory PSPs (EPSPs)
    • Depolarize neuron (make more +)
  • Inhibitory (IPSPs)
    • Hyperpolarize neuron (make more -)

NTs inactivated

  • Buffering
    • e.g., glutamate into astrocytes (Anderson & Swanson, 2000)
  • Reuptake via transporters
    • molecules in membrane that move NTs inside
    • e.g., serotonin via serotonin transporter (SERT)
  • Enzymatic degradation
    • e.g., AChE degrades ACh

Questions to ponder

  • Why must NTs be inactivated?

Questions to ponder

  • Why must NTs be inactivated?
    • Keeps messages discrete, localized in time and space

What sort of PSP would opening a Na+ channel produce?

  • Excitatory PSP, Na+ flows in
  • Excitatory PSP, Na+ flows out
  • Inhibitory PSP, Na+ flows in
  • Inhibitory PSP, Na+ flows out

What sort of PSP would opening a Na+ channel produce?

  • Excitatory PSP, Na+ flows in
  • Excitatory PSP, Na+ flows out
  • Inhibitory PSP, Na+ flows in
  • Inhibitory PSP, Na+ flows out

What sort of PSP would opening a Cl- channel produce?

Remember [Cl-out]>>[Cl-in]; Assume resting potential ~60 mV

  • Excitatory PSP, Cl- flows in
  • Excitatory PSP, Cl- flows out
  • Inhibitory PSP, Cl- flows in
  • Inhibitory PSP, Cl- flows out

What sort of PSP would opening a Cl- channel produce?

Remember [Cl-out]>>[Cl-in]; Assume resting potential ~60 mV

  • Excitatory PSP, Cl- flows in
  • Excitatory PSP, Cl- flows out
  • Inhibitory PSP, Cl- flows in
  • Inhibitory PSP, Cl- flows out

Types of synapses

Blausen 0843 SynapseTypes

Types of synapses

  • Axodendritic (axon to dendrite)
  • Axosomatic (axon to soma)
  • Axoaxonic (axon to axon)
  • Axosecretory (axon to bloodstream)

Synapses on

  • dendrites
    • usually excitatory
  • cell bodies
    • usually inhibitory
  • axons
    • usually modulatory (change p(fire))

Summary of chemical transmission

Neurotransmiters

Family Neurotansmitter
Amino acids Glutamate (Glu)
Gamma aminobutyric acid (GABA)
Glycine
Aspartate

Glutamate

  • Primary excitatory NT in CNS
  • Role in learning (via NMDA receptor)
  • Transporters on neurons and glia (astrocytes and oligodendrocytes)
  • Linked to umami (savory) taste sensation, think monosodium glutamate (MSG)
  • Dysregulation in schizophrenia? (Javitt, 2010)

Glutamate

Type Receptor Esp Permeable to
Ionotropic AMPA Na+, K+
Kainate
NMDA Ca++
Metabotropic mGlu

GABA

  • Primary inhibitory NT in CNS
  • Excitatory in developing CNS, [Cl-] in >> [Cl-] out
  • Binding sites for benzodiazepines (e.g., Valium), barbiturates, ethanol, etc.
Type Receptor Esp Permeable to
Ionotropic GABA-A Cl-
Metabotropic GABA-B K+

GABA

Other amino acid NTs

  • Glycine
    • Spinal cord interneurons
  • Aspartate
    • Like Glu, stimulates NMDA receptor

Acetylcholine (ACh)

  • Primary NT of CNS output
  • Somatic nervous system (neuromuscular junction)
  • Autonomic nervous system
    • Sympathetic branch: preganglionic neuron
    • Parasympathetic branch: pre/postganglionic
  • Inactivation by acetylcholinesterase (AChE)

ACh anatomy

Acetylcholine

Type Receptor Esp Permeable to Blocked by
Ionotropic Nicotinic (nAChR) Na+, K+ e.g., Curare
Metabotropic Muscarinic (mAChR) K+ e.g., Atropine

Curare

Atropine

How to stop your prey

Substance Effect
Japanese pufferfish toxin Blocks voltage-gated Na+ channels
Black widow spider venom Accelerates presynaptic ACh release
Botulinum toxin Prevents ACh vesicles from binding presynaptically
Sarin nerve gas Impedes ACh breakdown by AChE
Pesticides Impede AChE
Tetanus toxin Blocks release of GABA, glycine

Next time…

  • More on NTs!

References

Anderson, C. M., & Swanson, R. A. (2000). Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia, 32(1), 1–14. https://doi.org/10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W

Javitt, D. C. (2010). Glutamatergic theories of schizophrenia. Israel Journal of Psychiatry and Related Sciences, 47(1), 4.