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Dieter Jaeger Department of Biology Emory University djaeger@emory

How neurons integrate thousands of synaptic inputs each second. Dieter Jaeger Department of Biology Emory University djaeger@emory.edu. The textbook view. KSJ 4th ed., Fig. 10-7. Kandel, 4 th edition. In vivo input levels. 100 m m. 100 m m. GP neuron surface area: 17,700 m m 2

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Dieter Jaeger Department of Biology Emory University djaeger@emory

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  1. How neurons integrate thousands of synaptic inputs each second Dieter Jaeger Department of Biology Emory University djaeger@emory.edu

  2. The textbook view

  3. KSJ 4th ed., Fig. 10-7

  4. Kandel, 4th edition

  5. In vivo input levels 100 mm 100 mm • GP neuron • surface area: 17,700 mm2 • number of synapses (ex/in): 1,200 / 6,800 • number of inputs / s 12,000 / 6,800 • Ca3 pyramidal neuron • surface area: 38,800 mm2 • number of synapses (ex/in): 17,000 / 2,000 • number of inputs / s 170,000 / 20,000

  6. In vivo recording from striatal medium spiny neuron

  7. Coding with thousands of inputs each second

  8. Isyn = Gin * (Vm - Ein) + Gex * (Vm - Eex) Esyn = (Gin * Ein)+ (Gex * Eex) / (Gin+ Gex) Isyn = (Gin + Gex)* (Vm - Esyn) Isyn = (300 nS) * (60-50mV) = 3 nA 5,000 AMPA and 500 GABAA Synapses at 10 Hz Ein = -70 mV Eex = 0 mV

  9. dynamic current clamp DCN neuron patch pipette Isyn = Iex + Iin = Gex*(Vm-Eex) + Gin*(Vm-Ein) Isyn Vm AxoClamp 2B Vm slice, 32 C Isyn To apply in vivo like input

  10. Dynamic current clamping of GP neuron

  11. current versus conductance source Vm Esyn - 40 mV 5 mV Isyn outward Iexp 0 nA inward 0.2 nA 100 msec

  12. Input current Isyn outward Iexp 0 nA inward 0.1 nA 50 ms spike triggering events Input frequency 1.0 Input conductance input synchronization: 10 groups 100 groups 50 ms

  13. Small conductance K[Ca] current (Sk)

  14. The effect of Sk block on synaptic integration

  15. Space! The next frontier

  16. Shunting by somatic conductance

  17. Shunting by distributed conductance

  18. Functional Implications • synaptic conductance stabilizes Vm through shunting • spikes can only be triggered from transients • spikes reflect inputs correlated on the order of 1-10 ms • spike rate reflects correlation as well as input rate • inhibition has equal access to the control of spiking

  19. More complexity to come • gap junctions • short term plasticity (history dependence) • calcium signaling • dendritic spike initiation

  20. Acknowledgements Contributors: Volker Gauck Svetlana Gurvich Lisa Kreiner Mayuri Maddi Kelly Suter Other Lab Members: Alfonso Delgado-Reyes Jesse Hanson Chris Roland Simon Peron

  21. (Obeso et. al., Trends Neurosci 23(10):S8-S19, 2000) Current models of basal ganglia function determine spike rates based on simple summing of synaptic inputs NormalParkinson’s Disease

  22. cerebellar circuit cerebellar cortex Cerebellar cortex !? deep cerebellar nuclei DCN mossy fibers climbing fibers from Paxinos & Watson, "The rat brain', Academic Press

  23. The effect of synchronization 100 independent inputs 10 independent inputs 20 mV -50 mV 200 msec 200 msec

  24. 2.5 60 2.0 40 1.5 20 1.0 0 0.5 0.5 1 2 4 8 16 0.5 1 2 4 8 16 precision & rate spike timing precision spike frequency [%] [rel.] gain factor gain factor synchronization high intermediate none

  25. spiking in vitro and in vivo in vitro 20 mV 200 msec in vivo, awake (from LeDoux et al. 1998, Neuroscience, 86(2):533) time scale for coding: 500 msec 10 msec rate code temporal code

  26. Constructing in-vivo like synaptic input gmax: 2.1 pS - 69 pS gain 0.5 - gain 16 Gin: 1 nS at gain 1 Gex 30,100 UC’s/s 0.5 inhibitory unitary conductance 0 Esyn - 40 mV 10 mV 100 ms

  27. Shink and Smith, J. Comp. Neurol.358: 119-141 (1995)

  28. 100 mm ~100 mm • DCN neuron • surface area: 11,056 mm2 • number of synapses (ex/in): 5,000 / 15,000 • number of inputs / s 25,000 / 750,000 • Purkinje cell • surface area: 261,000 mm2 • number of synapses (ex/in): 175,000 / 5,000 • number of inputs / s 350,000 / 10,000

  29. 100 mm • Cerebellar Stellate cell • surface area: 2,305 mm2 • number of synapses (ex/in): 1,000 / 100 • number of inputs / s 2,000 / 200

  30. -70 mV = Eleak

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