Lecture 25: The tripartite synapse

Glial cells(glia)

• 10-50 times as many glia than neurons in the CNS

• PNS:

  • glia are made by schwann cells

  • make myelin for peripheral cells

• CNS:

  • microglia

  • oligodendrocytes

  • astrocytes

• ion channel expression: potassium channels(maintain resting mV close to equilibrium potential of potassium

Astrocytes

• most common type of glial cell in CNS

• found in grey and white matter

• interwoven with neurons

The tripartite synapse

consists of:

• presynaptic neuron

• postsynaptic neuron

• astrocytes

glutamate transporters

• clear glutamate from synapse

Astrocytic processes affect synaptic transmission

• astrocytes affect diffusion + uptake of NT from synaptic cleft

  • limits how far glutamate can go because of astrocyte reuptake

• shape/proximity of astrocytes isn’t stable

  • helps regulate duration and extense of glutamate presence in synapse

• can change within minutes

• changes across sleep-wake cycle

  • closer to neuron when awake

Astrocytic transporters for glutamate uptake

• EAAT: transporter that is electrogenic so you can record current change

  • 1 potassium out for every 1 Glutamate, 1 H+, and 3 Na+ in

Astrocytic glutamate transporter currents

• THA blocks all glutamate transporters so current is gone

• DHK: blocks ½ of glutamate transporter subtypes so current slightly decreases

GABA and Glycine transporters on astrocytes

• GLYT-1 and GAT regulate uptake on the astrocyte

Ion channels in astrocytes

• potassium channels

  • maintain normal levels of [K+] out

  • Drive Vm of astrocytes which is ~80mV aka close to the equilibrium potential of potassium

• Voltage gated ion channels

  • voltage gated sodium, chloride, and calcium channels

• other calcium channels

  • intracellular

  • mechano-sensitive

    • ion channel that responds to mechanical stimulation

• ion channel responds to depolarization with sodium, chloride, and calcium entry(not excitable enough for depolarization)

Electrically coupled groups of astrocytes

• astrocytes connected with other astrocytes through gap junctions

• groups of 50-100 electrically couples astrocytes can be regulated together

• groups of electrically coupled astrocytes tend to be somewhat exclusive, forming microdomains of 200-300 µm

• astrocytes with calcium sensitive dye, if you poke the pink one, calcium entry and it spreads to adjacent through gap junctions

• by 8 seconds calcium has spread throughout astrocyte microdomain

Release of glutamate from astrocytes

• calcium-dependent release from vesicles

• glutamate-transporters working in reverse

• glutamate conducting ion channels

• mechanical stimulation of astrocyte → increased calcium in glia → glutamate release in extrasynaptic space → activation of pre-synaptic mGluRs → less NT release due to mGluR inhibition of VGCC/alterations of SNARE proteins→ decreased EPSP amplitude

But are astrocytes involved in “information processing”?

• astrocytes respond to external signals from other elements of the nervous system, including neurons

• responses to external signals can change cytosolic calcium levels in astrocytes rapidly + at high temporal precision(microdomains)

• astrocytes release neurotransmitters in a calcium dependent manner

• release of neurotransmitter by astrocytes can affect neuronal responses