The Tripartite Synapse

What are glial cells?

* there are 10-50 times as many glial cells as neurons
* Peripheral nervous system
* glial cells are called Schwann cells
* make myeline for peripheral axons
* central nervous system
* microglia: birain-macrophages. Immune cells of the brain adn sometimes are called shape-shifters (bs astrocyte shappe normally and then changes to macrophage shape in response to tissue injury)
* oligodendrocytes: myelin providing structures in the brain
* astrocytes: glial cells that provide environmental and structural support and have the potential to participate in neuronal signaling. Astrocytes have alot of leak potassium ion channels
* ion channel expression: potassium ion channels are found in glial cells and thus the membrane maintain a resting membrane potential close to the equilibrium potential of potassium=very negative)

presynaptic trains of action potentials trigger….

a calcium increase in Schwann cells

* low frequency→ do not see any activity with the schwann cells
* if a burst of high frequency stimulus→ release enough transmitter to diffuse out to the parasynaptic locations and thus increase calcium release in Schwann cells

transmitters released from motor nerve terminals act on….

Schwann cell receptors to trigger signaling cacades

* Schwann cells express: L-type voltage gated calcium channels, Muscarinic ACh channels, Substance P receptos, ATP and adenosine purine receptors
* mAChR are linked to IP3 which project to the ER for more calcium release
* NK1 is the receptors for Substance P and it is a metabotropic receptors and itr triggers secondary messanger pathways

After GTP-gamma-s injection into Schwann cells…

neurotransmitter release is reduced

* influencing the GTP on the Schwann cell→ reduces NT release on motor neuron

After GDP-beta-S injection into Schwann cells…

a train of action potentials that normally leads to synaptic depression, now has less depression

* GDP-beta-s reduces G protein fucntions→ the motor neuron retains its ability to release neurotransmitter

Depending on the pattern of presynaptic activity, there are different intracellular calcium changes in Schwann cells, what are they?

Single response calcium activity or Oscillatory calcium response activity

What is the calcium response in Schwann cells when there is continuous activity? (stimulus)

* single response of Calcium
* continueous activity/release→ once calcium EPSP where there is one, robust response

What is the calcium response in Schwann cells when there is bursting activity?

* calcium activity is oscillatory
* bistinf activity/release→ waxing/waning type pattern of clacium inside schwann cell

What are astrocytes?

* most common types of glial cell in the CNS
* found in gray and white matter’

What is the tripartite synpase?

* a synapse contains three parts: the presynaptic neuron, the postsynaptic neurnon and the astrocytes
* astrocytes affect diffusion and reuptake of neurotransmitter in synaptic cleft→ isolates the synapse and “seals” it and so that the neurotransmitter can’t diffuse out of the synapse inot other synapses nearby

What are some astrocytic processes that affect synaptic transmission?

* astrocytes affect diffusion and uptake of neurotransmitter from the synaptic cleft
* shape/proximity of astrocytes is not stable
* can change over the course of minutes
* change across sleep-wake cycle
* sleep= seal less strong
* wake= more sealing off

What are the components for astrocytic transporters for glutamate uptake?

* glutamate entry on astrocytes is such that 1 potassium leaves for every one glutamate, proton, and 3 sodium that enter the astrocyte. This means that there is a net positive chart when glutamate is entering→ can record this current
* if block the glutamate transporters in astrocytes→ glutamate current goes away. The current does not reverse because it is not an ionic current, it is a transporter current and it only ever takes glutmate from the synapse and doesnt spit it back out (the IV plot will not ever cross the x-axis)
* note: astrocytes also have GLYT-1 and GAT transporters (for glycine and GABA)

What are the components on the ion channels in astrocytes?

* note: astrocytes are not electrocitable like neurons→ still has resting membrane potential, can hyoerpolarize or depolarize but will never be able to fire an action potential
* potassium ion channels
* maintain normal levels of \[K+} out
* drive Vm of astrocytes (\~-80mV)
* buffers on potassium to avoid excitotoxicity
* voltage gated ion channels
* voltage gates Na+ channels
* voltage-gated Cl- channels
* Voltage gates Ca++ channels
* other calcium ion channels
* intracellular channels : IP3 receptors on ER can trigger release Ca++ from ER to increase intracellular concentration of calcium
* mechano-sensitive channels: responds to pjysical stimuli in the environment as a response

\

What are eletrically-coupled groups of astrocytes?

* astrocytes are connected to other astrocytes via gap junctions
* groups of 50-100 electrically-coupled astrocytes can be regulated together
* these groups of electrically-coupled astrocytes tend to be somehwat exclusive, forming “microdomains” of 200-300 micrometers
* basically if calcium activates one, its evokes response from all coupled astrocytes in the microdomain

How can glutamate be released from astrocytes?

* astrocytes can release neurotransmitter
* calcium-dependent release from microvesicles from the astrocytes
* docked and released in calcium dependent manner
* glutamate transporters working in reverse→ if calcium is really high
* glutamate-conducting ion channels are presents
* glutamates from astrocytes can act on presynaptic metabotropic receptors to prevent more release of vesicles of glutamate from the axon terminals

Are astrocytes involved in “information processing”?

(4 points)

1. astrocytes response to external signals from other elements of the nervous system, including neurons
2. reponses to external signals can change sytosolic calcium levels inside astrocytes rapidly and at high temporal precision
3. astrocytes release neurotransmitters in a calcium-dependent manner
4. release of neurotransmitter by astrocytes can affect neuronal responses.