Astrocytes and the Tripartite synapse Flashcards
Astrocyte (4)
appearance + size + BV + location
- Star like property: The glial fibrillary acidic protein (GFAP) gives the astrocyte it’s star like shape
- Smaller then neurons
- 99.7% of astrocytes touch blood vessel and wraps around
- Tile the entire tissue, in grey matter and white matter. No where are there no astrocytes
Astrocytes morphology (3)
prob + solut
- Astrocytes have innumerable fine processes that fill a small sphere of brain tissue
- Glial fibrillary acidic protein (GFAP) is a highly expressed filament protein in astrocytes but it does not exist in the fine astrocyte processes (small, irregular branches that extend from astrocytes and make up a large portion of their plasma membrane)
- A plasma membrane anchored green flourescent protein “Ick-GFP” enables visualization of the full cell
Astrocyte spatial orientation with eachother
Each astrocyte has a domain territory taken up by the cell. Every astrocyte abuts a neighbouring astricyte and there is very little overlap between the porcesses of neighbouring cells. The degree of overlap is shown in yellow in the images on the right.
Astrocytes and it’s connectivity with eachother:
Astrocytes touch eachother in this way to form gap junctions from cell to cell. Thus, all astrocytes make up a vast syncytium with connected cytosols and the ability to move ions and small molecules through the astrocyte network.
Glial cells are largely:
non-excitable
- Very little response in astrocytes to the same current injection that makes neuronal memnrane potential change dramatically.
What occurs if you inject current in astrocytes?
mechanism
- The resting membrane potential of an astrocytes is very negative (-85mV). This is because astrocytes have a high permeability to K+ ions at rest and thus their membrane potential is close to the equilibrium potential of potassium (Ek).
- This gives them a low input resistance and makes them very leaky
What occurs if you inject current in astrocytes in terms of the IV curve
Astrocyte fine processes interact with synapses
Most of the tiny astrocyte processes are in close apposition to synapses to help support synaptic function. Astrocyte lack——. A single astrocyte makes extensive contacts with multiple dendrites or neurons. Estimated that the fine processes froma single astrocyte interact with 100K synapses.
- long processes that project to distant locations
Synapse and neuron somas are wrapped in:
Astrocyte fine processes
Astrocytes express a variety of transporters for NT. Explain the glutamate process:
- Glutamate clearance is especially pronounced and important via EAAT1 and 2
- EAAT use the driving force of Na+ to bring in glutamate
- Glutamate is converted to glutamine inside astrocytes via glutamine synthetase
- Glutamine is shuttled back to the presynapse for its reconversion and use in synaptic transmission
Net charge for EAATs:
Glutamate uptake through the EAAT generates ——- that can be recorded electrophysiologically in voltage camp.
- an inward Na+ current
EAATs are electrogenic —–
positive
The efficacy of glutamate uptake can shape neuronal excitability (2):
- Can impact post synapse: quicker mopped up by astrocytes then less synapse
- spill over
Explain this:
- Physically poking an astrocyte with a pipette initates a wave of Ca2+ elevation inside astrocytes that propagates as a wave
Explain the paracrine mechanism of astrocyte:
Transmitters like ATP or glutamate can start waves.
- ATP or glutamate puff can cause Gq coupled P2Y receptors which make IP3 that releases Ca2+ (exocytosis) at the ER in cytosol to elevate intracellular free Ca2+. This Ca2+ trigger snare to release ATP which diffuses out the cell (into extracellular) to the ATP channel of the next astrocyte. Additionally, IP3 and Ca2+ can diffuse through gap junction to the next astrocyte to release Ca2+.
Gap jumping with astrocytes:
Explain the role mGlur
Strong synaptic activity increases astrocyte free intracellular Ca2+ whereas weak synaptic activity does not cause an astrocyte signal. One needs lots of glutamate release to overcome uptake, spill out of the synapse and activate astrocyte mGluRs. So basically there is lots of glutamate released EEATs get saturated and glutamate binds with mGluR to activate calcium efflux.
Astrocytes respond to strong synaptic activity with:
an increase in free Ca2+ via mGluRs
Experimental techniques to stimulate astrocytes directly and measure effects in neurons:
- Photolysis of caged intracellular Ca2+ or IP3 in astrocytes using focal light stimulation has been used to demonstrate that astrocytes can communicate to neurons.
- Shine light which breaks caged Ca2+ and Ca2+ can travel and bind to flouresence which activates it.
endfoot
specialized compartment of the astrocyte that contacts the blood supply
domain architecture
formed because astrocyte fine processes do not overlap with neighboring astrocytes
which part of the astrocyte interacts with synapses?
the fine processes which makes extensive contacts with multiple dendrites
how do astrocytes communicate with each other?
through Ca2+ waves (involves activation of PLC which produces IP3 and releases intracellular Ca2+ stores)
how do astrocytes communicate across gaps, “gap jumping” ?
releases a diffusible messenger (ATP), this continues propagation of Ca2+ wave
strong synaptic activity can increase free intracellular Ca2+ in the astrocyte because:
increased glutamate spillage can activate astrocyte mGluR which activates IP3 pathway
BAPTA
buffers Ca2+ (calcium-chelating agent), blocks astrocyte signalling and prevents effects in neurons
Techniques to block astrocyte signalling and prevent effects in neuron (3):
How do we silence astrocytes to see neuorn activity?
Explain this experiment:
All synapses are encased in ——-. Astrocytes express a variety of G-protein coupled receptors (e.g., mGluRs, P2Y) and sense neurotransmitters by increasing free intracellular Ca²⁺. They respond to neurotransmitters by releasing gliotransmitters such as ——–. These gliotransmitters have a variety of actions on neural function, including direct effects on synaptic strength and facilitating long-term potentiation (LTP).
- astrocyte fine processes
- ATP, glutamate, or D-serine
