activity-dependent structural and functional plasticity of astrocyte-neuron interactions by: luís...
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Activity-Dependent Structural and Functional Plasticity of Astrocyte-Neuron Interactions
By: Luís Carvalho
Charles UniversityPhysiology29/04/09
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Astrocytes
- Number and structure according with complexity of the organism.
- Numerous in CNS.
- One astrocyte contacts 1000ssynapses.
- Enwraps 4-8 neuronal somata and 300-600 dendrites.
- Most prominent feature:Glial fibrillary acidic protein (GFAP).
Gray matter - protoplasmic
White matter - fibrous
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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-Riversideglial fibrillary acidic protein (GFAP)tagged with antibody.
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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))
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Tripartite Synapse
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Fellin et al., Physiology 21, 208 (2006)
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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
Metabolic support: provide neurons nutrients such as lactate
Astrocyte Role:
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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”
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- 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.
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-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
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Neuron to Astrocyte Signaling
I. Glutamate release from pre-synaptic neuron
II. Metabotropic receptors for Glutamate (mGluR) located on
astrocyte bind synaptic Glutamate. Subsequent
intracellular Phospholipase C release leads to Inositol
Triphosphate (InsP3) production.
III. Ion channels open, allowing vesicular-
bound pools of Ca2+ into the intracellular
enviornment.
IV. Intracellular levels of Ca2+ rise., free Ca2+ releases other
pools of vesicular-bound Ca2+.
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- Can be also caused by increased extracellular K+ levels.
- Modify gene expression and consequent morphological changes.
- Cause own release of glutamate. Further adjacent neuron activation. (not confirmed)
Ca2+ increase…
Basis of Matainance of microvascular tone
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Astrocytes are connected by gap junctions thereby forming a syncytium that is able to propagate signals for large distances
Ca2+ Increase cause…
- Wave propagation signal
- Mechanism of wave propagation viarelease of ATP to ECS > Activates neighboring cells.
- Thigh junctions. Not certain. Observed only in intense electrical stimulation
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Gliotransmission
Glutamate:
Post synaptic - contribute to network synchronization
Pre synaptic - facilitates subsequent glutamate release. Favoring neurotransmission - ionotropic receptors Inhibition - metabotropic receptors
Ca2+
Astrocyte
Glu
Ca2+
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Synchronous Firing Groups - Astrocytic Regulation of Neural Networks
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D serine
Important intermediary in glutamate neurotransmissiontogether with glutamate ionotropic receptors. Instead of glycine (hippocampus, retina, hypothalamus).
TNF - a
Promotes the neuronal insertion of AMPA receptors enhancing and maintaining synaptic strength.
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ATP and adenosine:
ATP - P2Y receptors in astrocytes.Triggers intracellular Ca2+ release and wave propagation. > GlutamateSignal 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.
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Astrocytic Mobility
- Constantly changing their morphology.
- Specially distal processes devoid of GFAP are extremely mobile.(GFAP imunolabelings show even in normal conditions)
Long term potentiation (LTP)Observed in Hippocampus - increase of density and closer apposition to synaptic cleft of potentiate synapses.Astrocyte Remodeling.
Examples:
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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
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Brain Stem
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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.
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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.
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Neuropathological conditions
Epilepsy - acompained by astrocyte hypertrophy and hyperplasia
Schizophrenia - astrocytes produce factors like Bornea disease virusPhosphoprotein 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.
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End! Thank you for your attention…
Bye!