Dieter Jaeger Department of Biology Emory University djaeger@emory

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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 - PowerPoint PPT Presentation

Transcript of Dieter Jaeger Department of Biology Emory University djaeger@emory

Dieter JaegerDepartment of Biology

Emory Universitydjaeger@emory.edu

KSJ 4th ed., Fig. 10-7

Kandel, 4th edition

100 m

100 m

GP neuron

• surface area: 17,700 m2

• number of synapses (ex/in): 1,200 / 6,800

• number of inputs / s 12,000 / 6,800

Ca3 pyramidal neuron

• surface area: 38,800 m2

• number of synapses (ex/in): 17,000 / 2,000

• number of inputs / s 170,000 / 20,000

In vivo input levels

In vivo recording from striatal medium spiny neuron

5,000 AMPA and 500 GABAA Synapses at 10 Hz

Ein = -70 mV

Eex = 0 mV

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

AxoClamp 2B

Isyn = Iex + Iin= Gex*(Vm-Eex)+ Gin*(Vm-Ein)

Vm

Isyn

Isyn Vm

dynamic current clamp

patchpipette

To apply in vivo like input

DCNneuron

slice, 32 C

Dynamic current clamping of GP neuron

current versus conductance source

100 msec

- 40 mV

0.2 nA

5 mV

0 nAoutward

inward

Vm

Esyn

Isyn

Iexp

spike triggering events

1.0

input synchronization:

10 groups100 groups

50 ms

Input frequency

Input conductance

50 ms0.1 nA

0 nAoutward

inward

Isyn

Iexp

Input current

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:

Volker Gauck

Svetlana Gurvich

Lisa Kreiner

Mayuri Maddi

Kelly Suter

Other Lab Members:

Alfonso Delgado-Reyes

Jesse Hanson

Chris Roland

Simon Peron

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):S8-S19, 2000)

DCN

from Paxinos & Watson, "The rat brain', Academic Press

Cerebellar cortex

deepcerebellar

nuclei

cerebellar cortex

mossy fibersclimbing fibers

!?

cerebellar circuit

-50 mV

20 mV

200 msec

The effect of synchronization

200 msec

100 independent inputs 10 independent inputs

spike timing precision

gain factor

spike frequency

synchronization highintermediatenone

0.5 1 2 4 8 16

2.5

2.0

1.5

1.0

0.5

0.5 1 2 4 8 16

0

20

40

60[%]

precision & rate

[rel.]

gain factor

200 msec

20 mV

spiking in vitro and in vivo

in vivo, awake (from LeDoux et al. 1998, Neuroscience, 86(2):533)

in vitro

500 msec 10 msectime scale for coding:

rate code temporal code

30,100 UC’s/s

inhibitory unitary conductance

Constructing in-vivo like synaptic input

100 ms

0.5

10 mV

0

Gex

Gin: 1 nS at gain 1

Esyn

- 40 mV

gmax: 2.1 pS - 69 pS gain 0.5 - gain 16

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

~100 m

100 m

Purkinje cell

• surface area: 261,000 m2

• number of synapses (ex/in): 175,000 / 5,000

• number of inputs / s 350,000 / 10,000

DCN neuron

• surface area: 11,056 m2

• number of synapses (ex/in): 5,000 / 15,000

• number of inputs / s 25,000 / 750,000

100 m

Cerebellar Stellate cell

• surface area: 2,305 m2

• number of synapses (ex/in): 1,000 / 100

• number of inputs / s 2,000 / 200

-70 mV = Eleak