PHYSL 371: Astrocytes

what are the main 3 types of astroglia

1. radial glia (embryogenesis)

2. protoplasmic astrocytes (grey matter)

3. fibrous astrocytes (white matter)

what are the 4 types of glial cells in the CNS

1. Astrocytes

2. Oligodendrocytes

3. Microglia

4. Ependymal cells

what does the notochord arise from

mesoderm

what do signals from the notochord cause

inward folding of ectoderm at the neural plate

what do the ends of the neural plate do

fuse together and disconnect from the ectoderm to form the neural tube

what does the neural tube become

(CNS) brain and spinal cord

what do the neural crest cells arise from

neural plate formation then branch off

what do neural crest cells become

peripheral nervous system

what is the inside of the neural tube called

ventricular zone

what is the outer layer of the neural tube called

Pia

where are radial glia located

start along the ventricular zone then migrate up towards the pia

what gives rise to radial glia

(NEC) neural epithelial stem cells

what do radial glia give rise to

more radial glia, neurons, and astrocytes

where do astrocytes originate from

radial glia cells (RGCs) at the ventricular zone

when do astrocytes originate

day 18 in embryonic mice or week 16-18 in human gestation

when does neurogenesis stop in gestation

around week 16-18 (when astrocyte development begins)

when does astrocyte production stop

postnatal day 7

what happens after astrocyte production stops

the astrocytes mature and ultimately tile the entire brain

what happens as astrocytes mature

they expand their territories until they experience contact inhibition and eventually form non-overlapping domains (only adjacent astrocytes interact at the margins of their territories)

what is the appearance of protoplasmic astrocytes

bushy/spongy in appearance

what type of network do astrocytes form

tiled networks and layers throughout the cortex

what are the 2 regional specializations of astrocytes

1. end-feet

2. PAPs (perisynaptic astrocyte processes)

what does imaging with the marker GFAP show

the end feet of astrocytes along a blood vessel

what is not able to be seen in imaging using the marker GFAP

PAPs (perisynaptic astrocyte processes) which are very small, adjacent to synapses, and require special imaging

protoplasmic astrocyte end-feet

ends of astrocytes that anchor to the basal lamina/basement membrane of a capillary

end-feet function

highly specialized with many channels to move water and other molecules in between the brain and blood in order to maintain homeostasis

what connects astrocytes together

gap junctions

why can't we use light microscopy to see PAPs

they are very small and therefore have poor resolution

what imaging technique is used instead to be able to view PAPs

electron microscopy (FIB-SEM)

PAPs (perisynaptic astrocyte processes)

small specialized structures that are in extremely close proximity to pre and post synaptic nerve terminals

tripartite synapse

The idea that a synapse includes not only the pre- and postsynaptic neurons involved but also encompasses many connections with PAPs

PAP function

has ion channels, many receptors, transporters (uptake and release), and other related machinery to release compounds

as we move higher in evolution, what happens to astrocytes

they increase in number and complexity

what could greater computational power of the human brain be due to

elaboration of astrocytes rather than elaboration of neurons

what are the 4 core homeostatic functions of astrocytes

1. molecular homeostasis

2. metabolic homeostasis

3. cellular and network homeostasis

4. systemic homeostasis

molecular homeostasis of astrocytes

ionic, CSF, neurochemical, and volume homeostasis

ionic homeostasis

astrocytes take up extraceullar K+ that increases due to neuronal activity

transmitter homeostasis

excitatory amino acid transporters (EAATs) will pull glutamate out of the synapse, turn it into glutamine, and deliver it back to the neuron so it can make more glutamate which prevents over excitation of the post synaptic cell and excitotoxicity (other transporters exist for GABA, adenosine, and lactate)

metabolic homeostasis of astrocytes

energy supply and blood flow homeostasis

energy supply homeostasis

glucose from the blood is taken up into the astrocyte and is stored as glycogen or turned into lactate to deliver to neurons as the energy substrate

blood flow homeostasis

a feedforward mechanism where neural activity causes blood vessels to dilate and supply O2 before O2 falls

what is the contractile element of arterioles

smooth muscle

what is the contractile element of capilaries

pericytes

how does the feedforward mechanism work

1. increased neuronal activity causes glutamate and ATP release at tripartite synapse

2. glutamate activates mGluRs or ATP activates P2Rs on the PAP

3. on the PAP, this leads to activation of 2nd messenger cascades causing an increase in AA (arachidonic acid)

4. at the end feet, AA is converted into PGE2 (prostaglandin)

5. PGE2 activates EP4 receptor on either the smooth muscle on arterioles or pericytes and capillaries

6. activation of EP4 receptor results in hyperpolarization and relaxation

7. relation causes vasodilation and increased blood flow

8. increased blood flow causes increased O2

cellular and network homeostasis of astrocytes

astrocytes contain multiple receptors , transporters, channels, and their own transmitter that work to regulate neuronal signalling and maintain brain homeostasis by controlling the levels of transmitters and signalling molecules in the CSF

gliotransmitter

Refers to a chemical (a neurotransmitter) that is released from an astrocyte and which binds to receptors on the postsynaptic neuron

examples of gliotransmitters

glutamate, GABA, D-serine, ATP

what is the mechanism of cellular and network homeostasis

1. when. the presynaptic neuron fires are releases transmitters, these affect receptors on the postsynaptic neuron AND the PAP

2. activation of PAP receptors triggers Ca2+ increase and gliotransmitter release via exocytosis

3. gliotransmitters act on astrocyte, pre and post synaptic neurons to modulate synaptic transmission, neuronal excitability, and plasticity