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Glial Signaling

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. Microglia

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Glial Signaling

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  1. Glial Signaling Astroglial Networks influence Information Processing

  2. What are Glia? • Glia is Greek for Glue • Support Cells • surround dendrites, soma, axons • Outnumber Neurons • 10 – 50X more glia • Housekeeping, Remove debris

  3. Types of Glia • Microglia • Phagocytes (from peripheral macrophages) • mobilized after injury/infection • Macroglia • Oligodendrocytes • Schwann Cells • Astrocytes

  4. Types of Macroglia • 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

  5. Types of Macroglia • 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

  6. Astroglia

  7. Blood Brain Barrier Tight Junctions

  8. Astroglial Networks • Astroglia express connexins (Cx) • Gap Junction (GJ) channels • Cx30 + Cx43 ≈ 50% each • GJ channels mediate • large cellular ensembles • circuit: 100s of astrocytes

  9. Cxs vs Receptors • Cxs= basic channel proteins • make up GJs • Evolutionary precursor for • Ion channels • Ionotropic Receptors • = ligand-gated ion channels

  10. Astroglial Networks • Extended Glial Circuits • Confer selective and preferential inter-astroglial connections • Not all neighboring astrocytes functionally connected by GJs • Functionally distinct glial populations

  11. Astroglial Networks • Similar to Neuronal Circuits • Finely organized • Anatomical/functional compartments • Short-term regulation • via molecules effecting GJ coupling • different expression of Cx30or Cx43

  12. Astroglial Networks • Functional Plasticity • GJ permeability/selectivity • Regulated by: Neuronal Activity • Neurotransmitters • Cannabinoids • Endothelins – constrict blood vessels

  13. Tripartite Synapse • Mechanism of Astrocyte synergism • active role in neurotransmission • Sense Neuronal inputs • via Ion Channels • Neurotransmitter Receptors • Neurotransmitter Transporters • Display Dynamic Signaling

  14. Tripartite Synapse • Controls Synaptic boundaries • limits volume

  15. Tripartite Synapse • Three WayInteractions

  16. Astroglial Networks + Tripartite SynapseAN + TS allow for: • TS Astrocytes • Take up Neurotransmitters • Glu • ATP • GABA

  17. AN + TS: Astrocytes • Take up Neurotransmitters • Glu • ATP • GABA

  18. 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

  19. 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

  20. AN + TS: Astrocytes • Make Neuropeptides • Angiotensin • ANP • EnK(opiate) • Dyn(opiate) • Galanin • NPY • Nociceptin (orphanin FQ) • OT • AVP • Somatostatin • SP • TachykininA • VIP

  21. AN + TS: Astrocytes • Make Neuropeptides • Angiotensin • ANP • EnK(opiate) • Dyn(opiate) • Galanin • NPY • Nociceptin (orphanin FQ) • OT • AVP • Somatostatin • SP • TachykininA • VIP

  22. AN + TS: Astrocytes • Bind Neurotransmitters (have receptors) • AMPA, NMDA, mGluR (Glu) • GABAA • 5-HT1A? • P2 (ATP) • Y1 (NPY), NK1 (SP) • TrKB (BDNF), bFGF • T3

  23. AN + TS: Astrocytes • Bind Neurotransmitters (have receptors) • AMPA, NMDA, mGluR (Glu) • GABAA • 5-HT1A • P2 (ATP) • Y1 (NPY), NK1 (SP) • TrKB (BDNF), bFGF • T3

  24. 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

  25. AN + TS: Astrocytes • Regulate Cellular/Synaptic Ions • Ca++ wave

  26. AN + TS: Astrocytes • Regulate Cellular/Synaptic Ions • extra/intra-cellular K+

  27. Astrocytes NetworksEffect 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

  28. Astrocytes NetworksEffect 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

  29. Astrocytes NetworksEffect 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

  30. Is there Anything That Astroglial Networks andTripartite Synapses Don’t Influence?

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