17 - Glial Cells

Question 1

What are the three types of glial cell?

Answer 1

Astrocytes

Oligodendrocytes

Microglial cells

(oligodendrocyte progenitor cell (precursor for oligodendrocytes))

Question 2

During disease how are glial cells altered?

Answer 2

Positive alterations: eg gain of function

Negative: Loss of function

Question 3

Astrocytes are uniquely positioned to support and influence the ______

Answer 3

Astrocytes are uniquely positioned to support and influence the synapse

Question 4

Astrocytes make extensive contacts with multiple ______

Answer 4

Astrocytes make extensive contacts with multiple dendrites

Question 5

Oligodendrocytes are the ______ cell of the CNS

Produce _______ wrapping substance

Answer 5

Oligodendrocytes are the myelinating cell of the CNS

Produce lipid-rich wrapping substance

Question 6

Astrocyte fine processes interact with _______

Answer 6

Astrocyte fine processes interact with synapses

Question 7

A single astrocyte has innumerable ________ that fill up a _______ in the brain

Answer 7

A single astrocyte has innumerable fine processes that fill up a spherical domain in the brain

Question 8

Astrocytes lack:

Answer 8

long processes that project to distant locations

Question 9

At the EM level astrocyte processes wrap

Answer 9

all synapses

-important in regulation of synaptic function

Question 10

Astrocytes at the synapses can sense _______ (and ______); important for getting rid of

Answer 10

Astrocytes at the synapses can sense glutamate and neuronal activity; important for getting rid of glutamate

Question 11

Astrocytes are rich with the glutamate transporter ______

Answer 11

Astrocytes are rich with the glutamate transporter GLT-1

Question 12

What happens when GLT-1 is put into a HEK cell (with patch clamping)

Answer 12

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

Question 13

Glutamate is _______ through astrocyte using the ______ transporter. Which can regulate:

Answer 13

Glutamate is recycled through astrocyte using the GLT-1 transporter.

Glutamate reuptake can regulate firing

Question 14

______ inhibits Glutamate reuptake transporters (eg Glt-1)

Answer 14

PDC inhibits Glutamate reuptake transporters (eg Glt-1)

Question 15

What effect does PDC have on the granule cell?

Answer 15

Prolonged spiking in granule cell in response to mossy fibre input

recall: PDC inhibits glutamate reuptake which can regulate firing

Question 16

Astrocytes express _____ receptors

Answer 16

Astrocytes express glutamate (NMDA/AMPA etc) and kainic acid receptors

Question 17

______ is a metabotropic glutamate receptor antagonist

Answer 17

MCPG is a metabotropic glutamate receptor antagonist

Question 18

When we stimulate Schaffer collateral (within hypothalamus) how does the astrocyte respond?

Answer 18

Ca++ changes within the astrocyte

astrocytes are responding to local neuronal activity

Question 19

Explain the image:

Stimulated Schaffer Collateral:

Spikes are _______

With ______ (antagonist to metabotropic Glutamate receptors)

Suggest glutamate receptors are important for regulating ______ in response to _______

Answer 19

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

Question 20

What co-agonists are required for NMDA receptor activity?

Answer 20

Glycine/D-Serine

Question 21

What happens if you clamp down Ca++ in astrocytes and then apply stimulation

Answer 21

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

Question 22

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 ________

Answer 22

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

Question 23

OPCs are located throughout the _______

Answer 23

OPCs are located throughout the CNS

Question 24

WHAT DO OPCs do that oligodendrocytes don’t?

Answer 24

OPCs synapse with neurons

Question 25

OPCs synapse with neurons How do we know?

Answer 25

* Stimulate schaffer collateral * measure putative OPC * induse biocytin (dye) with patch clamp * Evoked response happened in OPC

Question 26

Morphology of OPC in the image is similar to a \_\_\_\_\_

Answer 26

Synapse OPC's synapse with neurons - presumably a way to monitor neuronal activate

Question 27

Myelin increases the _____ of the membrane and decrease the \_\_\_\_\_\_

Answer 27

Myelin increases the _resistance_ of the membrane and decrease the _capacitance_ * prevents charges from leaving the axon

Question 28

Myelin can detect \_\_\_\_\_\_\_

Answer 28

Myelin can detect _axonal activity_

Question 29

NMDA receptors regulate ______ in oligodendrocytes

Answer 29

NMDA receptors regulate _glucose import/energy metabolism_ in oligodendrocytes

Question 30

Removing NMDA receptor (NR1) from oligodendrocytes and OPCs leads to:

Answer 30

Less glucose within the oligodendrocyte * axons fatigue faster (lower amplitude) and recover slower

Question 31

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

Answer 31

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

Question 32

Microglia respond to and sense their \_\_\_\_\_\_\_

Answer 32

Microglia respond to and sense their _environment_

Question 33

Microglial contribute to ________ during critical window

Answer 33

Microglial contribute to _synaptic pruning_ during critical window

Question 34

Synaptic pruning by microglia is _______ dependent

Answer 34

Synaptic pruning by microglia is _activity_ dependent

Question 35

Microglia monitor extracellular _____ (ie \_\_\_\_\_\_\_\_)

Answer 35

Microglia monitor extracellular _potassium_ (ie _neuronal activity_)

Question 36

Blocking the 2 pore K+ channel in microglia will reduce the \_\_\_\_\_\_\_

Answer 36

Blocking the 2 pore K+ channel in microglia will reduce the _current of ATP_ Suggests that ATP causes local K+ changes inside microglia

Question 37

Microglia are responsive to extracellular \_\_\_\_\_\_

Answer 37

Microglia are responsive to extracellular _potassium levels_

Question 38

Monitoring of potassium is likely a mechanism for microglia to sense the overal \_\_\_\_\_

Answer 38

Monitoring of potassium is likely a mechanism for microglia to sense the overall _neuronal activity_

Question 39

microglial knockout mice are much more susceptible to ____ when stimulated with kainate

Answer 39

microglial knockout mice are much more susceptible to _seizures_ when stimulated with kainate

Question 40

What is causing suppression of neuronal activity in microglial

Answer 40

neuronal activity → ATP → broken down into adenosine by microglia → adenosine suppresses activity

Question 41

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 _____ \_\_\_\_\_\_\_

Answer 41

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_ \_\_\_\_\_\_\_