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Signal processing in neurons

Signal processing in neurons. Metabotropic neurotransmission Electrical signals in dendrites Active properties of dendrites Signal processing at the Synapse (post) Dendrite Soma Synapse (pre). Neuronal Anatomy. Dendrites Input-spine Cell Body/Soma Axon Output-bouton. IN. MN a. Ia.

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Signal processing in neurons

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  1. Signal processing in neurons • Metabotropic neurotransmission • Electrical signals in dendrites • Active properties of dendrites • Signal processing at the • Synapse (post) • Dendrite • Soma • Synapse (pre)

  2. Neuronal Anatomy • Dendrites • Input-spine • Cell Body/Soma • Axon • Output-bouton

  3. IN MNa Ia MNb Agonist Antagonist Neural circuits, cartoon version • Spindle afferents excite the homonymous motor neuron and inhibit antagonists Inhibitory synapse Excitatory synapse

  4. Dendrite Morphology • Multiple synapses (10k+) • Multiple morphologies • Post-synaptic density VI Popov et al., 2004 Neuroscience

  5. Synaptic structure Garner 2002

  6. Input E/I PSPs • Synaptic strength • Efficiency of neurotransmitter release • Area/receptor number • Dendrite morphology • Input resistance • Membrane capacitance

  7. NMDA receptor mediated plasticity • Glutamineric synapses have both AMPA and NMDA receptors • Long term potentiation: Tetanus increases subsequent EPSPs • Tetanic depolarization relieves Mg2+ block (NMDA) • Calcium induced channel phosphorylation increases conductance • Long term potentiation • Ca2+ influx via NMDA receptors • DepolNMDACa2+CaMKIIAMPA • Ca2+(PKA)-|I1->PP1-|AMPA Low frequency stimulation Low Calcium I1 activates PP1 Decreases AMPA High frequency stimulation High Calcium I1 is inhibited Reduces PP1 Increases AMPA

  8. Metabotropic neurotransmission • GPCRs • Gs Adenyl Cyclase • AC->PKA->channel phos (NaV) • Gq phospholipase C • PLC->DAG->PKC->channel phos (AMPA) • Gbg GirK G-coupled inward rectifying potassium channel • Gbg CaV N, P, Q type voltage gated calcium channel • Slow – seconds to minutes

  9. Girk • Hippocampal neurons • GABAA channel • 1300 pA Cl- current • GABAB GPCR • 50 pA K+ current • Slow kinetics • Different GABAsensitivity • Cooperative currentsdifferent time Picrotoxin blocks GABAA Ba2+ blocks K+ GABAA GABAB Distinct I-V curves Different reversal potentials Sodickson & Bean 1996

  10. Recording Stimulation Metabotropic Neuromodulation • DSI stimulation triggers fast and slow depolarization • Slow depolarization is GTP dependent • Blocked by non-exchangeable GDP-b-S Fast Ionotropic depolarization Slow metabotropic depolarization Blocks metabotropic process

  11. mGluR1 suppression of m-current • M-Current: potassium current, near threshold, helps set excitability • After-hyperpolarization EPSPs recorded in CA3 neurons of guinnea pig DHPG is an mGluR agonist Prolonged exposure to DHPG results in sustained inactivation of m-current Brief exposure Long exposure Sustained, but not immediate suppression requires p38 MAP kinase Young S R et al. J Neurophysiol 2008;99:1105-1118

  12. Electrical interaction in dendrites • Local depolarization propagates • Internal resistance • Membrane capacitance • Time constants RC • Signal attenuation • Leak current Extracellular Cm Cm Rm Rm Ri Intracellular

  13. Active properties of dendrites • NaV • Low density prevents AP • PSP regeneration, amplification • CaV • T-type, low threshold • “Window current” bistatility • Additional calcium-mediated magic • Ih • Slow depolarization • Pacemaker

  14. Multiple inputs • Consider Unitary PSP 5 mV • Input current ~ 750pA = GV = G(0.060-(-0.060) • G=6250 pS (multiple channels at one synapse) • Simultaneous PSP • G=12,100pS • Input current 1500 pA • Second PSP during coincident wave: • G=6250; V=(0.06-(-0.055))= 115 mV • Input current = 720 pA • Dendritic branches isolate circuits

  15. Coincidence reinforcement • “Hebbian” plasticity • Neurons that fire together, wire together • Reinforcement of synapse consequent to AP • Back-propagation of AP, faster than PSP Stuart & Hauser, 2001

  16. Current interactions • Kleak • Ih (Nah) • LVA (CaT) • HVA (CaL) • KCa • KNa • NMDA • NaV • Kir • Cl • Multiple ions, multiple gatings • Local to synapse or distributed • Experimental models are incomplete: • Intact, decerebrate, isolated spine, slice, culture • Unique populations of neurons • See Grillner (2003); construct potential in a CPG or motor neuron w/nifedipine, stychnine, etc

  17. 5 4 Action Potential 3 2x Rheobase Stim Ampl (nA) 2 Chronaxie 1 Rheobase No Action Potential 0 0 0 . 2 0 . 4 0 . 6 0 . 8 1.0 1 . 2 1 . 4 1 . 6 1 . 8 2 Stim Duration (ms) Axon hillock • Integrates signals across dendritic tree • Dense NaV, highest probability of AP • Rheobase • Chronaxie

  18. Output Action Potential • Presynaptic inhibition • Ionotropic • Sub threshold depolarization of bouton • Reduce Ca2+ influx • Metabotropic • mGluR group II & IIII • Local NT release feeds back on presynaptic neruon

  19. Sea slug (tritonia) locomotion • Characteristic escape response • Alternate, vigorous body flexion • Simple neural circuit Lawrence & Watson 2002

  20. Flex Extend Dorsal Flexion Neuron Ventral Flexion Neuron Dorsal Swim Interneuron Ventral Swim Interneuron Tritonia CPG • Escape is a programmed response • Katz, et al., 2004 Intracellular potential of neurons Stimulate sensory neurons to elicit escape

  21. Recording Stimulation Tritonia Metabotropic Neuromodulation • DSI stimulation triggers fast and slow depolarization • Slow depolarization is GTP dependent • Blocked by non-exchangeable GDP-b-S Fast Ionotropic depolarization Slow metabotropic depolarization Blocks metabotropic process

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