Dieter Jaeger Department of Biology Emory University djaegeremory

Dieter Jaeger Department of Biology Emory University djaeger@emory. edu

KSJ 4 th ed. , Fig. 10 -7

Kandel, 4 th edition

In vivo input levels 100 mm GP neuron Ca 3 pyramidal neuron • surface area: 17, 700 mm 2 • surface area: 38, 800 mm 2 • number of synapses (ex/in): 1, 200 / 6, 800 • number of synapses (ex/in): 17, 000 / 2, 000 • number of inputs / s 12, 000 / 6, 800 • number of inputs / s 170, 000 / 20, 000

In vivo recording from striatal medium spiny neuron

5, 000 AMPA and 500 GABAA Synapses at 10 Hz Ein = -70 m. V Eex = 0 m. V Isyn = Gin * (Vm - Ein) + Gex * (Vm - Eex) Esyn = (Gin * Ein)+ (Gex * Eex) / (Gin+ Gex) Isyn = (Gin + Gex) * (Vm - Esyn) Isyn = (300 n. S) * (60 -50 m. V) = 3 n. A

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

Dynamic current clamping of GP neuron

current versus conductance source Vm Esyn - 40 m. V 5 m. V Isyn outward Iexp 0 n. A inward 0. 2 n. A 100 msec

spike triggering events Input frequency 1. 0 Input current Input conductance Isyn Iexp outward 0 n. A inward 0. 1 n. A input synchronization: 10 groups 100 groups 50 ms

Small conductance K[Ca] current (Sk)

The effect of Sk block on synaptic integration

Space! The next frontier

Shunting by somatic conductance

Shunting by distributed conductance

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

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

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

Current models of basal ganglia function determine spike rates based on simple summing of synaptic inputs Normal Parkinson’s Disease (Obeso et. al. , Trends Neurosci 23(10): S 8 -S 19, 2000)

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

The effect of synchronization 100 independent inputs 10 independent inputs 20 m. V -50 m. V 200 msec

precision & rate spike timing precision spike frequency [rel. ] 2. 5 2. 0 [%] 60 40 1. 5 20 1. 0 0 0. 5 1 2 4 8 16 gain factor synchronization high intermediate none

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

Constructing in-vivo like synaptic input gmax: 2. 1 p. S - 69 p. S gain 0. 5 - gain 16 Gin: 1 n. S at gain 1 Gex 30, 100 UC’s/s inhibitory unitary conductance 0. 5 0 Esyn - 40 m. V 100 ms

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

100 mm ~100 mm DCN neuron Purkinje cell • surface area: 261, 000 mm 2 • surface area: 11, 056 mm 2 • number of synapses (ex/in): 175, 000 / 5, 000 • number of synapses (ex/in): 5, 000 / 15, 000 • number of inputs / s 350, 000 / 10, 000 • number of inputs / s 25, 000 / 750, 000

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

-70 m. V = Eleak