N371: Astrocytes

What was the neurocentric view of glia?

Glia were thought to just “hold neurons together” (from Greek glue).

What’s the modern view of astrocytes?

They actively maintain the brain’s balance at molecular, metabolic, cellular, and systemic levels.

Main astroglial subtypes?

Radial glia, protoplasmic astrocytes, and fibrous astrocytes.

Function of radial glia?

Found only during embryogenesis; they produce neurons and later astrocytes from the ventricular zone of the neural tube.

Protoplasmic astrocytes – where and what do they do?

Gray matter; bushy, branched; surround synapses and blood vessels to regulate ionic and chemical balance.

Fibrous astrocytes – where and what do they do?

White matter; long, thin processes; provide structure and help axonal repair.

When do astrocytes form during development?

Around embryonic day 18 (E18) in mice, ~16–18 weeks in humans — after neurogenesis.

What happens as astrocytes mature?

They migrate outward and tile the brain with non-overlapping domains (contact inhibition).

What is “tiling”?

Each astrocyte occupies its own territory; neighboring astrocytes only touch at boundaries.

Do all astrocytes look and act the same?

No — structure and function vary by brain region! 😃

Are astrocytes electrically polarized like neurons?

No, but they have two special regions: endfeet and PAPs.

What do astrocytic endfeet do?

Wrap capillaries; anchor to the basal lamina; regulate water and ion flow via AQP4 and K⁺ channels. Each astrocyte has atleast 1

What is the neurovascular unit?

Astrocyte endfeet + endothelial cells + pericytes + neurons; maintains BBB and controls exchange between blood and brain.

How do endfeet communicate with each other?

Through gap junctions, forming a connected astrocyte network.

Do astrocytes generate action potentials?

❌ No! But membrane potential changes can still influence nearby cells through gap junctions.

What are PAPs?

Perisynaptic Astrocytic Processes—tiny (10–100 nm) branches wrapping around chemical synapses.

What’s the “tripartite synapse”?

Synapse composed of presynaptic + postsynaptic + astrocytic process.

PAP functions?

Clear neurotransmitters (esp. glutamate), prevent excitotoxicity, and modulate signaling.

What imaging is needed to see PAPs?

Serial electron microscopy (EM).

Marker used to identify astrocyte structure?

GFAP (glial fibrillary acidic protein).

Evolutionary trend of astrocytes? Why is this important?

Larger, more complex, and more numerous in advanced species; humans have ~1.1 glia/neuron (vs. 0.5 in mice). May underlie the greater computational power of the human brain.

Molecular homeostasis: what ions & molecules do astrocytes regulate? Why is this important?

Take up K⁺ (via Kir channels) from neuronal activity

Clear NTs from cleft. Uptake via EAATs (Excitatory Amino Acid Transporters). Glutamate converted to glutamine via glutamine synthetase → prevents over-excitation and allows neurons to keep firing safely.

Metabolic homeostasis – energy supply pathway?

Glucose → (astrocyte) glycogen or lactate → delivered to neurons for ATP production.

What’s neurovascular coupling?

When neurons become active, local blood vessels dilate → supply more O2 before O2 levels drop. 

Big take-home about PAPs and signaling?

Astrocytes listen and talk back — detect neuron firing (via Glu/ATP receptors), raise Ca²⁺, and release gliotransmitters (Glu, GABA, D-serine, ATP) to strengthen or weaken synapses.

What do PAPs have that help them do their job? 🤔

Ion channels, transporters, and receptors + machinery to take up or release signaling molecules

What is feedforward mechanism in neurovascular coupling?

1. Activity → GLU + ATP release → activate mGluRs/P2Rs on PAPs → second messenger cascades to raise [Ca2+] + [AA] (arachidonic acid)

2. End feet convert AA → PGE2 (protaglandin)

3. PGE2 activates EP4 receptor → end feet release vasoactive substances that act on smooth muscle cells (arterioles) or pericytes (capillaries)

4. Result: relaxation + vasodilation = more blood flow + O2 😀