Module IV - Lecture 2 - Glia

Question 1

To what extent do glia outnumber neurons and what role do they play and can they change function?

Answer 1

4:1, support role for neurons, and very dynamic and change function quickly

Question 2

Where do most glial cells come from?

Answer 2

radial glial cells following a gliogenic switch

Question 3

What are radial glial cells?

Answer 3

neural progenitor epithelial cells found in the embryonic neural tube and forebrain eventually become radial glial cells which can make more neurons and help neurons get to their final destination

Question 4

What is the embryonic neural tube?

Answer 4

primitive spinal chord

Question 5

What happens when a mitotic neuroepithelial cell divides?

Answer 5

one of the cells is a neuroepithelial cell and the sister cell goes on to become a neuron and this will continue to happen until the neurons pile up and then the neuroepithelial progenitor cells will become radial glial cells which can make more neurons ad help neurons get to their final destination

Question 6

When do neuroepithelial progenitor cells become radial glial cells that can produce more neurons through cell division and help these neurons reach their final destination?

Answer 6

embryonic day 9

Question 7

After making neurons what do radial glia cells undergo?

Answer 7

a gliogenic swicth and they become macroglia

Question 8

What type of precursors can radial glial cells turn into and what do they give rise to?

Answer 8

-oligodendrocyte precursor cells that turn into oligodendrocytes which myelinate the CNS
-can also turn into astricyte through an unknown precursor

Question 9

Where do CNS microglia come from?

Answer 9

stem cells in the embryonic yolk sac

Question 10

What do hematopoietic stem cells in the yolk sac turn into?

Answer 10

blood cells including primitive macrophage which then migrate to the CNS and turn into microglia (same source as immune cells)

Question 11

Where do glia of the PNS come from?

Answer 11

neural crest cells

Question 12

What do neural crest cell first make?

Answer 12

sensory dorsal root ganglion neurons (project into the periperhy and transmit sensory information) which undergo a gliogenic swicth

Question 13

AFter the gliogenic swicth what do neural crest cell make?

Answer 13

schwann cell precursors known as satellite glia

Question 14

What do satellite glia do?

Answer 14

cushion and protect cell bodies in the PNS and serve astrocyte like roles

Question 15

Where do schwann cell precursors migrate towards?

Answer 15

peripheral nerves and becomes myelinating shwann cells or remak cells which surround ,multiple axons and hold them close togetehr

Question 16

What are remak cells?

Answer 16

come from schwann cell precursors and they can surround multiple acons and hold them close together

Question 17

What is the most abunbdant cell type in the CNS and what three things to they do?

Answer 17

astrocytes
-trasnfer nutrients from blood vessles to neurons with activity
-can influence blood flow to regions to brain with more actuve neurons in response to NT release
-enhance the fidetlity of synaptic transmission (affect glutamatergic and inhibitory synaptogenesis by promoting or inhibiting it)

Question 18

What do astrocyte glutamate transporters do?

Answer 18

take up glutamate to prevent too much activation of postsynaptic neuorns

Question 19

What do astrocyte calcium permeable ampa receptors do?

Answer 19

they are activated by synaptic activity and result in astrocyte calcium waves that may signal enhanced high brain activity and are used to signal to blood vessels to increase blood flow to that area so there are a greater release of astrocyte mediated transfer of nutrients to active neurons

Question 20

What are astrocytes connected by?

Answer 20

gap junctions whcih have alot of cytoplasmic continuity between them and and they can contact up to 1000 synapses in the region

Question 21

How do astrocytes promote the function of glutamatergic synapses?

Answer 21

there are thrombospondins which are seceted by astrocytes and activate presynaptic calcium channels and the calcium signals help recruit presynaptic adhesion molecules presynaptic cell ashesion molecules like neurexins and they may also bind to postsynaptic neurligins directly to facilitate binding

Question 22

What kinds of synapses to thromobospondins secreted by astrocytes make?

Answer 22

they make silent synapses that lack AMPARs - these synapses do have NMDA receptors though - act at both the presynaptic and postsynaptic cell

Question 23

What is Hevin?

Answer 23

secreted by astrocytes and binds to presynaptic neurexins and and postsynaptic neurligins to promote their association and the development of excitatory synapses

Question 24

What kind of synapses does hevin make?

Answer 24

silent synapses that lack AMPAR but have NMDA

Question 25

What does SPARC do?

Answer 25

secreted by astrocytes and it may bind to and disrupt the ability of integrins to associate with the ecm proteins (lattice of proteins outside of synapses needed for proper positioning of synapses) and this results in an inhibition of synaptic development

Question 26

What are ECM proteins?

Answer 26

form an extracellular latticework of proteins outside of neurons that synapses may rely on for proper positioning

Question 27

How do astrocytes promote the maturation or unsilencing of glutamategric synapses?

Answer 27

they secrete glypican wehich binds to LAR receptors and promote the inertion of AMPA receptors in silent synapses

Question 28

What is the LAR receptor glypican binds to?

Answer 28

it is a tyrosine phosphatse which is coupled to trio and causes actin poylemtization adn synapses get larger allowing for more ampa to be inserted into the synapse

Question 29

If you culture astrocytes with neurons what happens to the number of exicitatory and inhibitory synapses you get? veruss if you culture neruons in the absence of astoryctes and what does this mean

Answer 29

-get more excitatory and inhibitory synapses if you culture the neurons with astrocytes and less if you do not culture them with astrocytes
-this means astrocytes are sufficient and necessary for synapse formation of inhibitory and excitatory synapses

Question 30

When are synapses eliminated and what happens if you eliminate too many synapses?

Answer 30

-adolescence
-schizophrenia

Question 31

What is responsible for synaptic pruning?

Answer 31

glia and microglia by squeezing between neurons and finding inactive synapses and phagocytozing them

Question 32

How does glia or microglia synaptic pruning work?

Answer 32

astrocytes secrete this unknown factor onto neurons that causes them to express a C1 complex and they cleave C3 complement proteins that are floating in the extracellualr space to produce iC3b which binds to inactive synapses and very actuve synpases express proteins that prevent ic3b from binding to them microglia have cr3 receptors which binds to ic3b to identify weak synapses and phagocytize them

Question 33

What is some proof that microglia phagocytosize presynaptuc terminals?

Answer 33

there are electron micrograph images of this

Question 34

What do microglia do in terms of spines?

Answer 34

they can encapsulate dendritic spines and turn them back into filopodia

Question 35

What also eats synapses and how?

Answer 35

astrocytes through the phagocytici recpetor Megf10 and MertK

Question 36

What changes in response to injury?

Answer 36

microglia and astrocytes

Question 37

How can astrocytes and microglia change their morphology for the good after injury?

Answer 37

can act as glutamate sponges with their GLUT transporters and take up glutamate released by dying neuron to prevent excitotoxicity and microglia can help break down bad or dying neurons

Question 38

How can astrocytes and microglia change their morphology for the bad after injury?

Answer 38

over proliferation of glial cells can cause a glial scar that acts as barriers for axon regeneration and resstebalishment of axon connections

Question 39

What myelinated axons in the cns and pns?

Answer 39

cns - oligodendrocytes promiscuous
pns - schwann cells

Question 40

What else can oligodendrocytes and schwann cells for?

Answer 40

they may help nourish neurons

Question 41

How can oligodendrocytes and schwann cells help nourish neurons?

Answer 41

myelin has MCT1 transporter which can shuttle lactate to neurons

Question 42

What can myelin regulation be?

Answer 42

a form of CNS plasticity in learning - degree of meylinating or spacing of nodes of rnavier

Question 43

What can schwann cells do post axon injury?

Answer 43

turn into pluripotent stem cells following axon injury to help break down damaged myelin and axons by releasing cytokine so macrophages can comes and chop up the axons and turn back into schwann cells that can form tunnel structures that can guid the new growth of an axon