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Key Events in the Formation of the BRAIN Initiative September 2011 – April 2013
Date Event Outcome Documents Dec 2011 Small group of
participants presents White paper to NIH, DARPA, and OSTP
Agenda PPT Presentation Group Photos
Page 1 of 1
Friday, December 16, 2011
10:00-‐11:30 NIH
Story Landis National Institute of Neurological Disorders and Stroke NINDS
12:30-‐1:30
DARPA Dr. Jay Schnitzer, DSO Director COL Christian Macedonia, DSO Program Manager Dr. Robert Colwell, MTO Deputy Director Dr. Timothy Broderick, MTO Program Manager
3:00-‐4:00
OSTP Tom Kalil Office of Science & Technology Policy OSTP
Participants Miyoung Chun George Church Jay Schnitzer Michael Roukes Rafa Yuste Story Landis Thomas Lee Tom Kalil
Pau l A l i v i s a to s Be r ke l e y / LBL
George Church Har va rd
Ra lph Green span UCSD/Kav l i
Michae l Roukes Ca l t e c h /Kav l i
Ra f ae l Yus te Co l umb i a /Kav l i Miyoung Chun Kav l i Founda t i on
FUNCTIONAL CONNECTOMICS: ���TOWARD AN ACTIVITY MAP OF THE BRAIN
Separate events leading up to today’s meeting:
¡ Sep 2010: Kavl i Pr ize Celebrat ion in Oslo, the idea to explore poss ib i l i t ies at the inter face between neurosc ience and nanosc ience is generated
¡ Sep 2011: Workshop on “Oppor tun i t ies at the Inter face of Neurosc ience and Nanosc ience” , i s he ld at Chicheley Hal l , UK – sponsored by Kav l i , Al len , and Gatsby Foundat ions
Outcome of the wor kshop: “The Bra in Act iv i ty Map Project” & emergence of five leading sc ient is ts in neurosc ience , nanosc ience , and systems bio logy
¡ Oct 2011: White paper & pre l iminar y technica l document are generated and submitted to OSTP; fur ther c i rcu lated to federa l funding agencies as wel l as other pr ivate foundat ions
¡ Dec 2011: In i t ia l meet ings to sol ic i t ear ly input f rom funding agencies
CONTEXT
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 2 16 Dec 2011
WE NEED NEW METHODS
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 3 16 Dec 2011
overarching goal: understanding how the brain works problem: emerging properties of brain function
“ What apparatus, in general terms, enables the brain to implement its remarkable performance?
The number of components (neurons) in the brain is probably about 1011 . The number of synapses, or contacts , between them is perhaps 1015 . On the average ever y neuron receives some thousands of dist inct inputs and itsel f connects to many other neurons.
The physical layout of most of the components is not par t icular ly neat .
How might one make some headway through this impossible jungle? ”
Franc is H Cr ick (1979) Think ing about the bra in .
Scient ific Amer ican 241: 219–232
Goal 1: Measure every action potential for every neuron in complete brain circuits
Goal 2: Manipulate the activity of every neuron in these circuits Goal 3: Computationally analyze/model these circuits Goal 4: (concurrent) Develop technological platforms to permit
scale-up to ever-larger hierarchical brain structures.
GOALS
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 4 16 Dec 2011
worm fly fish mouse
Goal 1: Measure every action potential for every neuron in complete brain circuits
GOALS (DETAILS)
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 5 16 Dec 2011
¡ Optical approach: Image act ion potent ia ls v ia Ca and voltage indicator ¡ Electrophysiologica l approach: 10k channels and upward ¡ Next-gen photonics-based s i l icon probes with nanopar t ic le indicator s
¡ Futur ist ic genomics approaches for reconstr uct ing act ion potent ia ls
Goal 1: Measure every action potential for every neuron in complete brain “circuits”
Goal 2: Manipulate the activity of every neuron in
complete brain circuits
GOALS (DETAILS)
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 6 16 Dec 2011
¡ Optogenet ics & caged compounds ¡ Nanopar t ic les coupled to nanoprobes ¡ Local chemical modulat ion through probe-based microfluidics
¡ Genetic str ategy
Goal 1: Measure every action potential for every neuron in complete brain “circuits”
Goal 2: Manipulate the activity of every neuron in
complete brain “circuits” Goal 3: Computationally analyze/model complete brain
circuits
GOALS (DETAILS)
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 7 16 Dec 2011
¡ Data reduct ion, management, and analys is ¡ Computat ional models to address brain c ircuit complexity
Goal 1: Measure every action potential for every neuron in complete brain “circuits”
Goal 2: Manipulate the activity of every neuron in
complete brain “circuits” Goal 3: Computationally analyze/model complete brain
“circuits” Goal 4: (concurrent) Develop technological platforms
to permit scale-up to ever-larger hierarchical brain structures.
GOALS (DETAILS)
¡ Fast , 3D imaging in scatter ing media ¡ Highly-mult ip lexed e lectrophys io log ica l recording (megaprobe project) ¡ Next-Gen photonic-based S i -probe plat form for deep st imulat ion & recording ¡ Mult iphys ica l measurements : imaging p lus voltage , chemica l & force “fields” ¡ Transform prototypes into robust instr umentat ion for neurosc ience community ¡ Novel Computat ional Approaches , mass ive data handl ing and storage
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 8 16 Dec 2011
¡ Scientific goals § Measure ever y spike to obtain a complete functional descr iption of the circuit (analogous
to the genome) § Decipher neural code: tackle the emergent proper ties of brain circuits § Solve connectivity diagrams: Reverse engineer neural circuits
¡ Medical goals § Develop novel assays for brain diseases § Emergent hypotheses for pathophysiology of brain disease
¡ Development of Powerful New Technology § Significant technological investment is cr itical; the project itself is l ikely to be the only
pr incipal near-term dr iver tech development
¡ Training of a new generation of interdisciplinary scientists
¡ Historical Precedents § In condensed matter physics: “More is Different” (P. Anderson; emergent proper ties) § Statistical mechanics, Magnetism, Dynamical Systems, Non-equilibr ium thermodynamics § Proven success of “big science” in molecular biology: The Human Genome Project
WHY?
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 9 16 Dec 2011
PARALLEL: HUMAN GENOME PROJECT
technology evolution
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 10 16 Dec 2011
Single investigator
Academic Center
Large-Scale Industrialization
Genome Center
PRECEDENT : GENOME PROJECT
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 11 16 Dec 2011
Genome Project : 20 to 200 researcher s per center. Modest Tech Development in Academic labs + tech transfer. One company inside (GTC) and one outside (Celera). Battel le repor t: 140-fold return on investment. SNP, HapMap, 1000 Genomes Project: Mainly deploying technologies. Several companies: Affymetr ix, I l lumina, LifeTech, CompleteGenomics. NHGRI $1000 genome: Aggressive Tech Dev: Broad tech por tfol io: dozens of academic star tups, large companies. Mil l ion-fold cost reduction in 7 year s.
ORGANIZATIONAL PRECEDENTS
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 12 16 Dec 2011
¡ Experimental neuroscientists explor ing worm, fish, mouse , rat , tur t le ,
…primates
¡ Computer scientists at the forefront of massive data mining technologies
¡ Computational neuroscientists bui lding models/analyses with next-gen complexity
¡ Chemists/biochemists developing nanopar t ic le and molecular repor ter s (for st imulat ion and recording)
¡ Nanoscientists ; and engage their key exper t faci l i t ies and staf f
¡ State-of-the-ar t microchip research foundries to translate “one-ofs” into prototypes capable of scale-up and production en masse
¡ Industrial partners to subsequently enable mass production and system integrat ion: enabl ing real izat ion and deployment of robust , integrated measurement instr uments
WHO MUST WE ENGAGE ���TO MAKE THIS HAPPEN?
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 13 16 Dec 2011
A DRAFT ROADMAP
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 14 16 Dec 2011
15 years: Entire brains behaving
10 years: 1 million neurons
5 years: 50,000 neurons
A DRAFT ROADMAP
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 15 16 Dec 2011
15 years: Entire brains behaving
10 years: 1 million neurons
5 years: 50,000 neurons
§ Example target circuits:
§ C. elegans § Mouse olfactor y bulb mitral cells § Mouse retinal ganglion cells § Mouse cor tical brain slice § …
A DRAFT ROADMAP
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 16 16 Dec 2011
15 years: Entire brains behaving
10 years: 1 million neurons
5 years: 50,000 neurons
§ Technology § Optical: achieve >100 Hz spike sampling § Electrophysiological: full 10kHz bandwidth § Typical time records: ~1h § Develop next-gen FAST optical voltage
repor ters (>1 kHz) § Computational optics § 3D Optogenetics
A DRAFT ROADMAP
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 17 16 Dec 2011
15 years: Entire brains behaving
10 years: 1 million neurons
5 years: 50,000 neurons
§ Example target circuits: § Drosophila § Mouse Retina § Zebrafish § Mouse hippocampus § Mouse cor tical area § Mouse models of disease § Etruscan Shrew cor tex
A DRAFT ROADMAP
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 18 16 Dec 2011
15 years: Entire brains behaving
10 years: 1 million neurons
5 years: 50,000 neurons
§ Example brain structures:
§ Entire cor tex in behaving mouse
§ Entire hippocampus in behaving rat
§ Cor tical area in awake pr imates
§ Human patients: brain-machine interface
A DRAFT ROADMAP
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 19 16 Dec 2011
15 years: Entire brains behaving
10 years: 1 million neurons
5 years: 50,000 neurons
§ Technology § Highly-multiplexed, Silicon neural
probes (shanks): large-scale integration § Photonic-based sensing: access
multiphysical “fields”
On#Chip(Fiber(Coupler(
Op0cal(Resonators((enable(Wavelength((Division(Mul0plexing)(
Integrated((Op0cal(Waveguide(
Separately#Addressable(Op0cal(EmiEer(“Pixels”(
External(Op0cal(Waveguide((from(Emission(Mul0plexer)(
Probe(Body(
Probe(Shanks(
Large Databases: Comparison ¡ Anatomic connectome
1500 neurons : 1×1013 raw pixels
So, 7×106 mouse cor t ical cel ls would be 50 ×1015 Bytes (= 50 PB)
¡ Genome image data per year wor ldwide: 30 PB .
¡ Astrophysics growing at 0.5 PB per year.
THE COMING DATA DELUGE
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 20 16 Dec 2011
1h time record
4 GB
200 TB
20 PB
Brain Activity Map – Raw Data Rates assume (5x5x5)=125 imaging voxels per cel l body
300 neurons at 12 bits/voxel at 50 Hz : ~ 180MB/s
50k neurons at 12 bits/voxel at 10 kHz : ~ 750 GB/s
7M cor t ical cel ls at 12 bits/voxel at 10kHz : ~105TB/s
1 bit
¡ Devices and techniques for diagnosing brain disorder s ear l ier and more accurately
¡ Strategies for fine control brain stimulation to rebalance diseased circuits
¡ Sensit ive , miniature , and intel l igent nanosystems for engineer ing and environmental applications
¡ Convergence of biotechnology and nanotechnology
¡ Development of new capabil it ies for storage and manipulation of massive datasets
¡ Development of novel, biological ly-inspired, computational devices.
LARGER BENEFITS
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 21 16 Dec 2011
¡ Functional , rather than structural , dynamic connectome
¡ Not a disembodied “Blue Brain” Model, but real data
¡ Completely open access to data
¡ Collaborative , rather than competit ive
¡ Develop, deploy next-gen instrumentation to community
CONTRAST W/ OTHER INITIATIVES
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 22 16 Dec 2011
¡ We can coordinate funding suppor t among var ious resources ranging from Federal Funding Agencies, Pr ivate Foundations, and Industr y
COLLABORATION AMONG ���FUNDING AGENCIES
NIH
DARPA Initiation of the Brain
Activity Map
Private Foundations
Industry
NSF
Others
Project Completion
¡ Santa Monica Kavl i Workshop: Milestones and Specific Aims
§ Januar y 28-30, 2012
§ Participants
§ Organizers:
§ Paul Alivisatos, George Church, Ralph Greenspan, Michael Roukes, & Rafa Yuste
§ Neuroscience:
§ Karl Diesseroth, Eve Marder, Thanos Siapas, Christof Koch, A.S. Chiang, & Sebastian Seung
§ Nanoscience:
§ Hongkun Park, Andreas Tolias, & Oskar Painter,
§ Imaging:
§ Xiaowei Zhuang, & Scott Fraser
NEXT STEPS?
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 24 16 Dec 2011
¡ WE NEED YOUR ADVICE: § Large Scale: too large for Grants or Foundations. Big Science
§ Interdisciplinar y Effor t
§ Repercussions for Science and Society
§ Ensure Public Buy-in
§ Ensure open access to all data § Human Genome Like Project
WHERE DO WE GO FROM HERE?
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 25 16 Dec 2011
NEW TOOLS
“ New directions in science are launched by new tools much more often than by new concepts.
The effect of a concept-dr iven revolution is to explain old things in new ways.
The effect of a tool-driven revolution is to discover new things that have to be explained. ”
Freeman Dyson (1997) Imagined Wor lds
Har vard Univer s i ty Press , Cambr idge , MA
Alivisatos, Church, Greenspan, Roukes, Yuste, Chun - (c) 2011 26 16 Dec 2011
THANK YOU