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 I. Microglia  Phagocytes (from peripheral macrophages)  mobilized after injury/infection II. Macroglia  Oligodendrocytes  Schwann Cells  Astrocytes

4. 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

5. 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

6. Astroglia

7. Blood Brain Barrier Tight Junctions

8. Astroglial Networks  Astroglia express connexins (Cx)  Gap Junction (GJ) channels  Cx 30 + Cx 43 ≈ 50% each  GJ channels mediate  large cellular ensembles  circuit: 100s of astrocytes

9. Cx s vs Receptors  Cx s = basic channel proteins  make up GJ s  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 Cx 30 or Cx 43

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.  Controls Synaptic boundaries  limits volume Tripartite Synapse

15.  Three Way Interactions Tripartite Synapse

16. Astroglial Networks + Tripartite Synapse AN + 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 (TNF α )  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 (TNF α )  homocysteic acid, taurine

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

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

22. AN + TS: Astrocytes  Bind Neurotransmitters (have receptors)  AMPA, NMDA, mGluR (Glu)  GABA A  5-HT 1A?  P 2 (ATP)  Y 1 (NPY), NK 1 (SP)  TrK B (BDNF), bFGF  T 3

23. AN + TS: Astrocytes  Bind Neurotransmitters (have receptors)  AMPA, NMDA, mGluR (Glu)  GABA A  5-HT 1A  P 2 (ATP)  Y 1 (NPY), NK 1 (SP)  TrK B (BDNF), bFGF  T 3

24. AN + TS: Astrocytes  Regulate Cellular/Synaptic Ions  Ca ++ Signaling  Initiated by Receptor Binding  e.g. mGluR, NK 1, Y 1  G p/q → PLC → PIP 2 → IP 3 → 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 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

28. 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

29. 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

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