17 - Glial Cells Flashcards
What are the three types of glial cell?
Astrocytes
Oligodendrocytes
Microglial cells
(oligodendrocyte progenitor cell (precursor for oligodendrocytes))
During disease how are glial cells altered?
Positive alterations: eg gain of function
Negative: Loss of function
Astrocytes are uniquely positioned to support and influence the ______
Astrocytes are uniquely positioned to support and influence the synapse
Astrocytes make extensive contacts with multiple ______
Astrocytes make extensive contacts with multiple dendrites
Oligodendrocytes are the ______ cell of the CNS
Produce _______ wrapping substance
Oligodendrocytes are the myelinating cell of the CNS
Produce lipid-rich wrapping substance
Astrocyte fine processes interact with _______
Astrocyte fine processes interact with synapses
A single astrocyte has innumerable ________ that fill up a _______ in the brain
A single astrocyte has innumerable fine processes that fill up a spherical domain in the brain
Astrocytes lack:
long processes that project to distant locations
At the EM level astrocyte processes wrap
all synapses
-important in regulation of synaptic function
Astrocytes at the synapses can sense _______ (and ______); important for getting rid of
Astrocytes at the synapses can sense glutamate and neuronal activity; important for getting rid of glutamate
Astrocytes are rich with the glutamate transporter ______
Astrocytes are rich with the glutamate transporter GLT-1
What happens when GLT-1 is put into a HEK cell (with patch clamping)
GLT-1 brings in glutamate as well as ions
GLT-1 in hek cell → can see that cells respond electrophysiologically based on level of glutamate
→ suggests that astrocytes sense glutamate
Glutamate is _______ through astrocyte using the ______ transporter. Which can regulate:
Glutamate is recycled through astrocyte using the GLT-1 transporter.
Glutamate reuptake can regulate firing
______ inhibits Glutamate reuptake transporters (eg Glt-1)
PDC inhibits Glutamate reuptake transporters (eg Glt-1)
What effect does PDC have on the granule cell?
Prolonged spiking in granule cell in response to mossy fibre input
recall: PDC inhibits glutamate reuptake which can regulate firing
Astrocytes express _____ receptors
Astrocytes express glutamate (NMDA/AMPA etc) and kainic acid receptors
______ is a metabotropic glutamate receptor antagonist
MCPG is a metabotropic glutamate receptor antagonist
When we stimulate Schaffer collateral (within hypothalamus) how does the astrocyte respond?
Ca++ changes within the astrocyte
astrocytes are responding to local neuronal activity
Explain the image:
Stimulated Schaffer Collateral:
Spikes are _______
With ______ (antagonist to metabotropic Glutamate receptors)
Suggest glutamate receptors are important for regulating ______ in response to _______
Explain the image:
Stimulated Schaffer Collateral:
Spikes are rises in Ca++ levels within astrocyte
With MCPG (antagonist to metabotropic Glutamate receptors)
Suggest glutamate receptors are important for regulating calcium levels in response to neuronal activity
What co-agonists are required for NMDA receptor activity?
Glycine/D-Serine
What happens if you clamp down Ca++ in astrocytes and then apply stimulation
You won’t get LTP
Astrocytes are responding to activity and releasing D-Serine (necessary for NMDA receptor activity which triggers LTP)
For LTP to occur must have astrocytes present and the capacity to respond to neuronal activity
Astrocyte Summary:
Neuronal synapses and somas are wrapped in _______
Astrocytes uptake and recycle ______
Glutamate uptake can shape _______
Astrocytes are excitable during neuronal activity - measured by ________
Astrocytes Ca is necessary for LTP through the release of ________
Astrocyte Summary:
Neuronal synapses and somas are wrapped in astrocyte processes
Astrocytes uptake and recycle glutamate
Glutamate uptake can shape neuronal excitability
Astrocytes are excitable during neuronal activity - measured by intracellular Ca
Astrocytes Ca is necessary for LTP through the release of D-Serine
OPCs are located throughout the _______
OPCs are located throughout the CNS
WHAT DO OPCs do that oligodendrocytes don’t?
OPCs synapse with neurons
OPCs synapse with neurons
How do we know?
- Stimulate schaffer collateral
- measure putative OPC
- induse biocytin (dye) with patch clamp
- Evoked response happened in OPC
Morphology of OPC in the image is similar to a _____
Synapse
OPC’s synapse with neurons - presumably a way to monitor neuronal activate
Myelin increases the _____ of the membrane and decrease the ______
Myelin increases the resistance of the membrane and decrease the capacitance
- prevents charges from leaving the axon
Myelin can detect _______
Myelin can detect axonal activity
NMDA receptors regulate ______ in oligodendrocytes
NMDA receptors regulate glucose import/energy metabolism in oligodendrocytes
Removing NMDA receptor (NR1) from oligodendrocytes and OPCs leads to:
Less glucose within the oligodendrocyte
- axons fatigue faster (lower amplitude) and recover slower
OPC/Oligodendrocyte Summary:
- ______ make oligodendrocytes but likely have several other roles
- OPCs monitor ________ activity through ______
- Myelin speeds _______
- Myelin/oligodendrocytes monitor ______, couple ________ and transmit _____ to axons
OPC/Oligodendrocyte Summary:
- OPCs make oligodendrocytes but likely have several other roles
- OPCs monitor axonal activity through OPC synapses
- Myelin speeds axonal conduction
- Myelin/oligodendrocytes monitor axonal activity, couple axonal activity to glucose import and transmit nutrients to axons
Microglia respond to and sense their _______
Microglia respond to and sense their environment
Microglial contribute to ________ during critical window
Microglial contribute to synaptic pruning during critical window
Synaptic pruning by microglia is _______ dependent
Synaptic pruning by microglia is activity dependent
Microglia monitor extracellular _____ (ie ________)
Microglia monitor extracellular potassium (ie neuronal activity)
Blocking the 2 pore K+ channel in microglia will reduce the _______
Blocking the 2 pore K+ channel in microglia will reduce the current of ATP
Suggests that ATP causes local K+ changes inside microglia
Microglia are responsive to extracellular ______
Microglia are responsive to extracellular potassium levels
Monitoring of potassium is likely a mechanism for microglia to sense the overal _____
Monitoring of potassium is likely a mechanism for microglia to sense the overall neuronal activity
microglial knockout mice are much more susceptible to ____ when stimulated with kainate
microglial knockout mice are much more susceptible to seizures when stimulated with kainate
What is causing suppression of neuronal activity in microglial
neuronal activity → ATP → broken down into adenosine by microglia → adenosine suppresses activity
Microglia summary:
- Microglia monitor the ____ and respond hundreds or thousands of factors
- Microglia contribute to _____ and _____
- Microglia monitor neuronal activity in part via levels of extracellular _____
- Absence of microglia predisposes mice to _____ due to microglia _____ _______
Microglia summary:
- Microglia monitor the CNS and respond to hundreds or thousands of factors
- Microglia contribute to synaptic pruning and development
- Microglia monitor neuronal activity in part via levels of extracellular potassium
- Absence of microglia predisposes mice to epilepsy due to microglia supressing neuronal activity _______
