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Glial Signaling Astroglial Networks influence Information Processing What are Glia? Glia is Greek for Glue Support Cells surround dendrites, soma, axons Outnumber Neurons 10 – 50X more glia Housekeeping, Remove debris Types of Glia I. Microglia Phagocytes (from peripheral macrophages) mobilized after injury/infection II. Macroglia Oligodendrocytes Schwann Cells Astrocytes Types of Macroglia 1. Oligodendrocytes / Schwann Cells small insulate axons Oligodendrocytes in Central NS 15 axonal internodes each Schwann Cells in Peripheral NS only 1 internode per Schwann cell Types of Macroglia 2. Astroglia – most numerous star-shaped soma long processes with end feet very similar to neurons end feet interface with neurons & synapses – tripartite synapse Create Blood-Brain Barrier Astroglia Blood Brain Barrier Tight Junctions Astroglial Networks Astroglia express connexins (Cx) Gap Junction (GJ) channels Cx30 + Cx43 ≈ 50% each GJ channels mediate large cellular ensembles circuit: 100s of astrocytes Cxs vs Receptors Cxs = basic channel proteins make up GJs Evolutionary precursor for Ion channels Ionotropic Receptors = ligand-gated ion channels Astroglial Networks Extended Glial Circuits Confer selective and preferential inter-astroglial connections Not all neighboring astrocytes functionally connected by GJs Functionally distinct glial populations Astroglial Networks Similar to Neuronal Circuits Finely organized Anatomical/functional compartments Short-term regulation via molecules effecting GJ coupling different expression of Cx30 or Cx43 Astroglial Networks Functional Plasticity GJ permeability/selectivity Regulated by: Neuronal Activity Neurotransmitters Cannabinoids Endothelins – constrict blood vessels Tripartite Synapse Mechanism of Astrocyte synergism active role in neurotransmission Sense Neuronal inputs via Ion Channels Neurotransmitter Receptors Neurotransmitter Transporters Display Dynamic Signaling Tripartite Synapse Controls Synaptic boundaries limits volume Tripartite Synapse Three Way Interactions Astroglial Networks + Tripartite Synapse AN + TS allow for: TS Astrocytes Take up Neurotransmitters Glu ATP GABA AN + TS: Astrocytes Take up Neurotransmitters Glu ATP GABA AN + TS: Astrocytes Release Neurotransmitters Activity-dependent manner more release as signal increases Glu ATP D-Serine Atrionatriuretic Factor (ANP) Tumor Necrosis Factor alpha (TNFα) homocysteic acid, taurine AN + TS: Astrocytes Release Neurotransmitters Activity-dependent manner more release as signal increases Glu ATP D-Serine Atrionatriuretic Factor (ANP) Tumor Necrosis Factor alpha (TNFα) homocysteic acid, taurine AN + TS: Astrocytes Make Neuropeptides Nociceptin (orphanin FQ) Angiotensin OT ANP AVP EnK (opiate) Somatostatin Dyn (opiate) SP Galanin TachykininA NPY VIP AN + TS: Astrocytes Make Neuropeptides Nociceptin (orphanin FQ) Angiotensin OT ANP AVP EnK (opiate) Dyn (opiate) Somatostatin SP Galanin TachykininA NPY VIP AN + TS: Astrocytes Bind Neurotransmitters (have receptors) AMPA, NMDA, mGluR (Glu) GABAA 5-HT1A? P2 (ATP) Y1 (NPY), NK1 (SP) TrKB (BDNF), bFGF T3 AN + TS: Astrocytes Bind Neurotransmitters (have receptors) AMPA, NMDA, mGluR (Glu) GABAA 5-HT1A P2 (ATP) Y1 (NPY), NK1 (SP) TrKB (BDNF), bFGF T3 AN + TS: Astrocytes Regulate Cellular/Synaptic Ions Ca++ Signaling Initiated by Receptor Binding e.g. mGluR, NK1, Y1 Gp/q → PLC → PIP2 → IP3 → Ca++ Propagated by GJ channels AN + TS: Astrocytes Regulate Cellular/Synaptic Ions Ca++ wave AN + TS: Astrocytes Regulate Cellular/Synaptic Ions extra/intra-cellular K+ Astrocytes Networks Effect via Tripartite Synapses Defines Specific Circuitries Functionally/Behaviorally essential Limits Synaptic Volume Focuses and Enhances Transmitters ↑ Efficiency of Reuptake / Recycling Regulates K+ availability -Influences progression of depolarization Astrocytes Networks Effect via Tripartite Synapses Produces/Secretes Gliotransmitters Neuropeptides & Trophic Factors Responds to Transmitters, Trophic Factors, and Neuropeptides Influences/Guides Ca++ Activity in Glia and Neurons +Impacts Progression of Action Potentials Guides Neurocircuit Activity Astrocytes Networks Effect via Tripartite Synapses Guides Neurocircuit Activity Synaptic Plasticity Influences Adaptive Behavior Spatial Memory, Motor Coordination, Sensorimotor Adaptation, Exploration, Stress Responses Impacts Cognitive & Neurological Disorders Spreading Depression (Migraine), Anxiety, Depression, Fear, Epilepsy Is there Anything That Astroglial Networks and Tripartite Synapses Don’t Influence?