Neurobiology Seminar

Activity-Dependent Structural and Functional Plasticity

of Astrocyte-Neuron Interactions

Jithin Krishnan
2019/PhD
 Astrocytes

-   Number and structure according

with complexity of the organism.

- Numerous in CNS.

- One astrocyte contacts 1000s

synapses. Gray matter - protoplasmic
- Enwraps 4-8 neuronal somata and
300-600 dendrites.

- Most prominent feature:

Glial fibrillary acidic protein (GFAP).

White matter - fibrous

Processing information is not an exclusive property of neurons…

-  Not only structural and nutritional

support. (Brain blood barrier)

- Role in regulation of synaptic

function.

- Can also undergo remodeling.

(Plasticity)

- The fine distal processes are

interposed between all neuronal
elements.

- Create a kind of synaptic island

defined by its ensheathing V. Parpura, UC-Riverside
processes. glial fibrillary acidic protein (GFAP)
tagged with antibody.
 Tripartite Synapse

- Considered a physical barrier to

restrict spill over and diffusion of
released molecules to ECS.

- Position of relevance to their

functions.

(Araque et al., TINS 22 (1999))

Tripartite Synapse
Fellin et al., Physiology 21, 208 (2006)
Astrocyte Role:
Metabolic support: provide neurons nutrients such as lactate

As Neural activity there is an Energy requirement

To solve this…
Astrocytic uptake of Glutamate leads to> ADP leads to> Glycolysis within Astrocytic
endfeet which finally leads to> Lactate delivered to neuron
Regulation of ion concentration in the ECS:

Ex: High number of K+ channels (high permeability).

Transference of K+ to sites of lower accumulation. High levels of K+ in ECS
would change neuronal exitability.

Clear neurotransmitters (glutamate and GABA):

Astrocytes have distal processes rich in transporters that remove excess

neurotransmitters (especially glutamate)
If Glutamate is not removed:
Diffuses into the ECS. Presynaptic bind and inhibition of its own release.
Influence other synapses - “Intersynaptic cross-talk”
- Secrete large complex substances to the ECS: Important as
structural elements and cell to cell communication.
Ex: Promotion of the myelinating activity of oligodendrocytes through
release of cytokine leukemia inhibitory factor (LIF).

- Nervous system repair: upon injury to nerve cells within the central
nervous system, astrocytes become phagocytic to ingest the injured nerve
cells. The astrocytes then fill up the space to form a glial scar, repairing
the area and replacing the CNS cells that cannot regenerate.
- Vasomodulation: Restrict access
of neurosecretory terminals to
perivascular basal lamina. (blood
flow)

Control the effect of

paracrine/autocrine secreted
peptides.

Regulate neurosecretion.
- Modulation of synaptic transmission
 Neuron to Astrocyte Signaling

IV. Intracellular levels

of Ca2+ rise., free
Ca2+ releases other
pools of vesicular-
bound Ca2+.

II. Metabotropic receptors for

Glutamate (mGluR) located on
astrocyte bind synaptic Glutamate. III. Ion channels open,
Subsequent intracellular allowing vesicular-bound
Phospholipase C release leads to pools of Ca2+ into the
Inositol Triphosphate (InsP3) intracellular enviornment.
production.

I. Glutamate release from pre-synaptic

neuron
Ca2+ increase…

- Can be also caused by increased extracellular K+ levels.

- Modify gene expression and consequent morphological changes.

Basis of Matainance of micro vascular tone

- Cause own release of glutamate.

Further adjacent neuron activation. (not confirmed)
Ca2+ Increase cause…

- Wave propagation signal

- Mechanism of wave propagation via

release of ATP to ECS > Activates
neighboring cells.

- Thigh junctions. Not certain.

Observed only in intense electrical
stimulation
Astrocytes are connected by gap 
junctions thereby forming a syncytium 
that is able to propagate signals for large 
distances
Gliotransmission

Glutamate:
Astrocyte
Post synaptic - contribute to network
synchronization
Ca2+

Pre synaptic - facilitates subsequent Ca2+

glutamate release.
Favoring neurotransmission - ionotropic Glu

receptors
Inhibition - metabotropic receptors
Synchronous Firing Groups - Astrocytic Regulation of Neural Networks
D serine

Important intermediary in glutamate neurotransmission

together with glutamate ionotropic receptors. Instead of
glycine (hippocampus, retina, hypothalamus).

TNF - a 

Promotes the neuronal insertion of AMPA receptors

enhancing and maintaining synaptic strength.
ATP and adenosine:

ATP - P2Y receptors in astrocytes.

Triggers intracellular Ca2+ release and wave propagation.
> Glutamate
Signal neighboring neurons by pre/post synaptic purinergic
receptors.

Converted to adenosine by ectonucleotidases in ECS.

Suppression of synaptic transmission.
A1/A2 receptors activation leads to positive action of K+
channels and negative action of Ca2+ channels.
Astrocytic Mobility

- Constantly changing their morphology.

- Specially distal processes devoid of GFAP are extremely mobile.

(GFAP imunolabelings show even in normal conditions)  

Examples:

Long term potentiation (LTP)

Observed in Hippocampus - increase of density
and closer apposition to synaptic cleft of
potentiate synapses.
Astrocyte Remodeling.
 Neuropathological conditions

Epilepsy - acompained by astrocyte hypertrophy and

hyperplasia

Schizophrenia - astrocytes produce factors like Bornea disease

virus
Phosphoprotein which have been linked to bahavioral
abnormalities in mice.

Astrocytes activated by injury - regulation of synaptic activity

and strength.
Importance in development of inflammatory pain.