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Signal processing in neurons

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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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