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Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego

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Page 1: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolving Brains

Terrence Sejnowski

HHMISalk Institute

University of California, San Diego

Evolving Brains

Terrence Sejnowski

HHMISalk Institute

University of California, San Diego

Page 2: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Levels of InvestigationLevels of Investigation

Page 3: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

“Nothing can be understood in Biologyexcept in the light of evolution”

T. Dobzhansky, 1973

“Nothing can be understood in Biologyexcept in the light of evolution”

T. Dobzhansky, 1973

Page 4: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Francis CrickJames Watson

“Nothing can be understood in Biologyexcept in the light of DNA”“Nothing can be understood in Biologyexcept in the light of DNA”

Page 5: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Natural SelectionNatural Selection

Page 6: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

DifferentiationDifferentiation

Page 7: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

DNA MethylationDNA Methylation

Page 8: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Neurons Reactivate a DNA MethylationProcess from Pluripotent Stem Cells

Neurons Reactivate a DNA MethylationProcess from Pluripotent Stem Cells

R. Lister*, E.A, Mukamel* et al.. Science (2013)

Fraction oftotal mC

Highly methylatedin all cell types

Assumedunmethylated

Page 9: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Neurons Accumulate DNA Methylation (mCH) During Brain Development

Neurons Accumulate DNA Methylation (mCH) During Brain Development

*DeFelipe et al. (1997); Huttenlocher et al., (1997)

R. Lister*, E.A, Mukamel* et al.. Science (2013)

Page 10: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Precise Patterns of mCHPrecise Patterns of mCH

R. Lister*, E.A, Mukamel* et al.. Science (2013)

Page 11: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Gene Expression is Correlated with mCHGene Expression is Correlated with mCH

Page 12: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

M. Margarita BehrensM. Margarita Behrens Eran MukamelEran Mukamel

Ryan ListerRyan ListerJoe EckerJoe Ecker

Page 13: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of Body SegmentsEvolution of Body Segments

Page 14: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of Ion ChannelsEvolution of Ion Channels

Page 15: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of PhotoreceptorsEvolution of Photoreceptors

Page 16: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of VisionEvolution of Vision

Page 17: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of SynapsesEvolution of Synapses

Page 18: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Brain InnovationBrain Innovation

Page 19: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of the CortexEvolution of the Cortex

Page 20: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of the CortexEvolution of the Cortex

Page 21: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of VisionEvolution of Vision

Page 22: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Evolution of VisionEvolution of Vision

Page 23: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Felleman and Van Essen,1991

Evolution of VisionEvolution of Vision

Page 24: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

A Tale of Two VolesA Tale of Two Voles

Montaine

Prairie

Young, Nilsen, Waymire, MacGregor and Insel, 1999

Repetitive expansion

Montane

Prairie

Page 25: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

KE Family Tree

Evolution of LanguageEvolution of Language

Page 26: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood
Page 27: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Cerebellum

Inferior Olive

Caudate Nucleus

Thalamus

Cortical Plate

Substantia Nigra

Inferior Olive

Page 28: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Sydney Brenner

Page 29: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

What Makes Humans Human?What Makes Humans Human?

Page 30: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood
Page 31: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

DenisovanNeanderthalPresurfer

Page 32: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

What Makes Humans Human?• Language• Hypersociality• Joint attention • Learning• Writing

Page 33: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood
Page 34: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

John Allman

Page 35: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

John Allman

Page 36: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Human BrainHuman Brain

Page 37: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Zhang and Sejnowski, 2000

Page 38: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Single Cell MethylomesSingle Cell Methylomes

Page 39: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Deep LearningDeep Learning

Page 40: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Picture CaptioningPicture Captioning

Page 41: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Picture CaptioningPicture Captioning

Page 42: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Dopamine NeuronsDopamine NeuronsActor Critic ModelActor Critic Model

Environment

Dopamine

Reward Prediction Error

Cerebral Cortex

BasalGanglia

Montague, Dayan and Sejnowski, 1996

Page 43: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood
Page 44: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

I should have shown a better result, a better outcome, and better content in terms of the game played, and I do apologize for not being able to satisfy a lot of people’s expectations. I kind of felt powerless.

Page 45: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

March 11, 2016: “AlphaGo can't beat me”

Ke Jie of ChinaKe Jie of China

Page 46: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

January 5, 2017: “After humanity spent thousands of years improving our tactics, computers tell us that humans are completely wrong.”

Ke Jie of ChinaKe Jie of China

Page 47: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

BRAIN InitiativeBrain Research through Advancing

Innovative Neurotechnologies

April 2, 2013

BRAIN InitiativeBrain Research through Advancing

Innovative Neurotechnologies

April 2, 2013 April 2, 2013

Page 48: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Advisory Committee to the NIH Director 

BRAIN 2025Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Working Group

JUNE 05, 2014

Page 49: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

Brain Activity Map

Page 50: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood

BRAIN InitiativeBRAIN Initiative

Page 51: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood
Page 52: Evolving Brains - Limes The... · Evolving Brains Terrence Sejnowski HHMI Salk Institute University of California, San Diego. Levels of Investigation “Nothing can be understood