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Exploring Neuronal Networks In Vivo

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Page 1: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Exploring Neuronal Networks In Vivo

Page 2: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Input / output

Page 3: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Layer

Page 4: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

What’s up, Brain?

Page 5: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

‘Cognition is an emergent property of anatomy’

Let’s copy it!

Page 6: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

I: Reverse Engineering

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Reverse engineering steps

• Assess physiology

Page 8: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Determining transfer function

MorphologyNeurotransmitter

Plasticity...

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Determining transfer function

Jiang, Science, 2015

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Reverse engineering steps

• Assess physiology

• Reproducing circuits neuron by neuron

• Feed it with relevant input

Page 11: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

C. Elegans

302 neurons

Openworm

Page 12: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

C. Elegans

Page 13: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

C. Elegans

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Mammals: the BlueBrain Project

Markram, EPFL

Page 15: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Blue Brain Project Limitations

The project’s current reconstructions reproduce [...] asmall part of the neocortex of young rats (about one third

of a cubic millimetre of cortical tissue).

In fact, the BBP’s latest reconstruction [...] representing

less than 1% of the synaptic connections in the circuit.

Markram, EPFLEuropean Human Brain Project: ~ 1.3 Billion Euros

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IBM output

IBM website

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II. Encoding

Wilson, 1993

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How are neuronal networks representing information?

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Neuroscientist Toolbox

Monitor neuronal networks

Neuronal scale: in space and time

Synchronise complex behavior: in space and

time

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Resolution is critical

EEG MRI

=measure of blood-flow oxygen levels

Page 21: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Electrodes

Max Planck Institute

We measure Volts! (microVolts)

Page 22: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Electrodes

Max Planck Institute

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Tetrodes

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Tetrodes

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Silicon probes

1

2

3

4

5

6

7

8

1

2

3

4

5

6

7

8

Buzsaki64, NeuroNexus

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Calcium-imaging

Motor cortex M1 of running mouseDaniel Huber 2009, Svoboda Lab, JFRC

Page 27: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Behavioral setups

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The Task

Kepecs, 2013

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• Extract rules of cognitive processing

– > What is represented in the brain?• Stimulus / Reward / Decision / Self-evaluation /

Memories?

How is it encoded?

– > What are the dynamics of learning?

Page 30: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Reward prediction

Example for one neuron

Schultz, 1997

Page 31: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

Reward prediction

Schultz, 1997

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Reward prediction

Schultz, 1997

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Reward prediction

Schultz, 1997

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Reward prediction

Schultz, 1997

Error message

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Topics of interest

• Cognitive flexibility

• Decision-making (gambling task)

• Spatial navigation

• Meta-cognition (confidence)

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At a network level

Yassa, 2013

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Dynamic properties

Colgin, 2016

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III. Meant to be?

Somogyi, 2013

Page 39: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

How about the neuronal types?

Kepecs, 2014

Page 40: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

How about the neuronal types?

Kepecs, 2014

Page 41: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

How about the neuronal types?

Kepecs, 2014

Page 42: Exploring Neuronal Networks In Vivo Lagoun - Exploring Neural... · Blue Brain Project Limitations The project’s current reconstructions reproduce [...] a small part of the neocortex

How about the neuronal types?

Kepecs, 2014

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Optogenetics

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Optogenetic tagging

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Control information flow

Répertoire of neurons ‘Fit to function’

Pi, 2013

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Connectivity

Network operation

Behavioralengagement

Type of neuron

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Building Bridges

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Thank you ;)

[email protected]