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Charles University
Physiology
29/04/09
Activity-Dependent Structural and Functional Plasticity
of Astrocyte-Neuron Interactions
By: Luís Carvalho
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 processes.
V. Parpura, UC-Riverside
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 vesicularbound Ca2+.
II. Metabotropic receptors for
Glutamate (mGluR) located on
astrocyte bind synaptic Glutamate.
Subsequent intracellular
Phospholipase C release leads to
Inositol Triphosphate (InsP3)
production.
I. Glutamate release from pre-synaptic
neuron
III. Ion channels open,
allowing vesicular-bound
pools of Ca2+ into the
intracellular enviornment.
Ca2+ increase…
- Can be also caused by increased extracellular K+ levels.
- Modify gene expression and consequent morphological changes.
Basis of Matainance of microvascular 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
Pre synaptic - facilitates
subsequent glutamate release.
Favoring neurotransmission ionotropic receptors
Inhibition - metabotropic
receptors
Ca2+
Ca2+
Glu
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.
Substances like OT are release by
neurohypophysis in times of parturition,
lactation or chronic dehydration.
Astrocytes - significant reduce coverage of
OT neurons.
Neurons- Somata hypertrophy, branch of
dendrites and axons enlarge and ramify.
Juxtaposed surfaces and dendrites
Brain Stem
Cerebellum
Bergmann glia require constant input
from their associated synapses to
maintain their relationship.
AMPA receptors (also for glutamate) +
GLuR2 subunit are responsible for
Ca2+ permeability.
Removal of the subunits reduced
permeability and provoked retraction of
glia.
Consequences of Extracellular Homeostasis
Any structural change in astrocyte environment should affect
properties of ECS.
Observing on rats.
During lactation:
Significant reduction of volume
fraction and tortuosity (diffusion rate
compared with obstacle-free medium)
Diffusion became equivalent in
all planes (isotropy, instead of
anisotropy in normal conditions)
Diffusion properties changed as well.
Enhance the range of action of molecules.
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.
End!
Thank you for your attention…
Bye!