3 - Synaptic Transmission

Question 1

How many chemical synapses does a typical CNS neuron fire or receive?

Answer 1

Tens of thousands

Question 2

Synaptic steps broken down

Answer 2

Presynaptic action potential reaches terminus
Ca2+ is released in the bouton
Neurotransmitter is exocytosed into synaptic cleft
Neurotransmitter activates postsynaptic receptors
Postsynaptic action potential (excitatory) is produced

Question 3

Two types of chemical synaptic receptors

Answer 3

Ionotropic Receptors

Metabotropic Receptors

Question 4

Ionotropic Receptors

Answer 4

Ligand-gated ion channels.
Binding of neurotransmitter induces conformational change, opening ion channel pore, allowing influx or efflux of ions, leading to membrane depolarization or hyperpolarization

Question 5

Metabotropic Receptors

Answer 5

Trigger 2nd messengers regulating ion channel activity indirectly.

Question 6

Ionotropic Receptors - Speed, Effect, Location

Answer 6

Fast (milliseconds)
Excitatory or Inhibitory
Localized within synapse

Question 7

Metabotropic Receptors - Speed, Effect, Location

Answer 7

Slow (hundreds of milliseconds - seconds - minutes)
Regulate excitability of postsynaptic neurons (alters resting membrane potential, or duration/threshold of postsynaptic action potential)

Question 8

Homosynaptic Plasticity???

Answer 8

The activity of the nerve terminal itself can alter release properties at the synapse

Question 9

Heterosynaptic Plasticity

Answer 9

Modulatory neuron releases modulatory neurotransmitter onto presynaptic nerve terminal.

Question 10

Types of Heterosynaptic Plasticity

Answer 10

Presynaptic Inhibition

Presynaptic Faciliation

Question 11

Presynaptic Facilitation

Answer 11

Modulatory neurotransmitter inhibits presynaptic K+ channels, prolonging the action potential.

Question 12

Neuromuscular Junction Synapse - Steps

Answer 12

Motor Neuron release Acetyl Choline

Acetyl Choline activates Nicotinic Acetyl Choline receptors on postsynaptic membrane (muscle)

Question 13

Curare

Answer 13

Poison on the heads of arrows in Central and South America.
Binds nicotinic Acetylcholine receptors (competitive inhibition)
Reduces excitatory action potential depolarization
No muscle contraction
Asphyxia (diaphragmatic paralysis)

Question 14

Nicotinic ACh Receptor

Answer 14

Ligand gated cation channel, permeable to most cations (Na+, K+, Ca++)
Predominantly drives cations in.
Depolarization.
Excitatory action potential.

Question 15

Nicotinic ACh Receptor - Structure

Answer 15

Pentameric membrane protein
Composed of 4 Homolygous subunits (Delta, Beta, Gamma, two Alpha) - each with 4 transmembrane domains and an extracellular N & C terminus

Question 16

Myasthenia Gravis

Answer 16

Autoimmune
Ab bind Nicotinic ACh receptors, reducing density of expression of Nicotinic receptors on surface
Leads to muscle weakness

Question 17

Congenital Myasthenic Syndrome

Answer 17

Genetic mutation in Nicotinic ACh Receptor in neuromuscular junction

Question 18

Stretch Reflex Circuit (Extensor as an example)

Answer 18

Extensor muscle spindle sensory neuron activated by stretch
Releases glutamate onto extensor motor neuron within spinal cord.
Excitatory postsynaptic action potential leads to muscle contraction

Question 19

Glutamate

Answer 19

Excitatory neurotransmitter

Question 20

Inhibitory Circuit (When Extensor is stretched)

Answer 20

Muscle spindle afferent nerve fibers synapse on inhibitory interneurons.
These fire an inhibitory action potential on the Flexor muscle

Question 21

Neuromuscular Junction Excitatory Neurotransmitter

Answer 21

Acetylcholine

Question 22

Spinal Cord Excitatory Neurotransmitter

Answer 22

Glutamate

Question 23

Inhibitory Neurotransmitters (Interneurons)

Answer 23

Gamma-Aminobutyric Acid (GABA)

Glycine

Question 24

Activation of GABA or Glycine receptors leads to

Answer 24

Hyperpolarization of the cell membrane (preventing action potentials from firing)

Question 25

2 Classes of Ligand-Gated Ionotropic Receptors

Answer 25

GABA/Glycine receptors

Question 26

GABA-A & Glycine Receptors

Answer 26

Antimeric
Permeable to Cl-
Allows Cl- influx
Leads to Membrane Hyperpolarization

Question 27

Nicotinic Acetylcholine Receptors

Answer 27

Antimeric
Excitatory
Similar to GABA/Glycine, but not permeable to Cl-

Question 28

Which drugs act through the GABA receptor, increasing and prolonging duration of inhibitory currents, and enhanced hyperpolarization?

Answer 28

Barbituates
Benzodiazepines
Alcohol
General Anesthetics

Question 29

Glutamate Receptors

Answer 29

Tetramer (Distantly related to K+ Channels)
3 Transmembrane Domains per subunit
Extracellular N-Terminus
Intracellular C-Terminus

Question 30

3 Families of Ionotropic Glutamate Receptors

Answer 30

AMPA Receptor (non-NMDA)
Kainate Receptor (non-NMDA)
NMDA

Question 31

AMPA Receptor

Answer 31

Permeable to Na+, K+
Channel opened by binding of Glutamate molecule
Located in Postsynaptic Membrane Surfaces
Responsible for fast glutamatergic response

Question 32

Kainate Receptor

Answer 32

Permeable to Na+, K+
Channel opened by binding of Glutamate molecule
Located in Presynaptic terminal

Question 33

NMDA

Answer 33

Permeable to Na+, K+
High Ca++ Permeability
Channel opened by binding of 2 Glutamate & 1 Glycine
There is enough Glycine in CSF, though, that functionally, these channels depend more on Glutamate release
Mg++ can plug ion channel pore, blocking ion flux, even when channel is open.
Depolarization evicts the Mg2+.
Effectively, NMDA receptors respond to the combination of ligands AND voltage.
Located on postsynaptic membrane surface
PCP (Angel Dust) can lead to NMDA hyperfunction.

Question 34

AMPA vs NMDA

Answer 34

AMPA action potentials rise and fall more quickly
NMDA rises and falls more quickly
At further depolarized states, Mg++ is not an issue anymore, so NMDA is more active.

Question 35

Long Term Depression (With respect to synapses)

Answer 35

AMPA receptors removed from postsynaptic membrane surface