synapses coursera lecture#1
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7/17/2019 Synapses Coursera Lecture#1
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Synapses, neurons and brains
I dan Segev
Lesson #1
Brain excitements for the 21st century
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Kick start
• Great thinkers think about the brain
• How it (us) all started?
• Brain Blossom worldwide
• Structure of modern brain-research centers
• The problem with “understanding the brain”
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"You, your joys and sorrows, your
memories and your ambitions, your sense
of personal identity and your free will are in
fact no more than the behavior of a vastassembly of nerve cells and their
associated molecules"
(Francis Crick, Nobel Laureate 1962 – “the
father of DNA”).
"Machine think? You bet! We’re machines and we
think, don’t we?" (Claude Shannon – “the father of information age”)
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“ he most
incomprehensible thing
about the world is that it
is at all comprehensible
So what is the route to comprehend the brain?
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The start
Or
3.5 Billion years of life on earth
The Homo sapiens sapiens
&
The ~ 100 years old “Human Brain Project”
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3.5 Billion years
Life begins - Bacteria
500 Million years
Fish
300 Million years
Reptiles
200 Million years
Mammals
70 Million years
Primates
200,000 years
Humans
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The development of mammalian “big brains”
200 Million years - TODAY
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800
900
1000
1100
1200
1300
1400
1500
00.20.40.60.811.21.41.6.8
Millions
Millions of years ago
B r a i n w e i g h t ( g r )
C u l t u r a l e v o l u t i o n
Modern Humans ~ 200,000 years & Cultural Evolution
Culture explosion of Homo sapiens sapiens
Language/Math
5,000 years
Science
3,000 years
Modern Computers
70 years
Art
(60,000 - 30,000 ago)
Cell Phones, ICT
Today
Understanding/rep
airing our brain
Today
Million years
B r a i n
w e i g h t - g r
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1. Brain Blossom Worldwide
The Jerusalem Brain
(Norman Foster)
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A view from the inside (of the brain)
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Quantitative Analysisof Neuronal circuits
Plasticity & DevelopmentalNeuroscience
Computational
&theoreticalNeuroscience
Human & PrimateBehavior and Cognition
Neuroscience ofNeurological & cognitiveDisorders
Structure of modern brain centers & central role of theory
(+ new curriculum for “Leonardo da Vinci” brain-researchers)
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Theory/Modeling
Neurobiology &Medicine
Computer Science
Psychology
Applied Physics & Engineering
The “da Vinci” generation of brain researchers
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Perspective: Some new dramatic ($ billions) projects for the brain
1. Allen Institute – Seatle, USA (Mouse/Human brain atlas – recently new
focus on mouse vision)
2. Janelia farm – DC, USA (Industrial scale Inst. for connecting network
level anatomy and physiology to s specific behavior)
3. EU Human Brain Project - EPFL, Lausanne Switzerland (ICT-based brain
research platform, integrating data and knowledge from different disciplines,
and catalyzing world-wide effort to achieve understanding of the brain,
propose new treatments for brain diseases and new brain-like computing
technologies) - Lesson #7.
4. President Obama’s “Brain Activity Map” initiative (Creating revolutionary
tools to measure/stimulate millions or even billions or neurons
simultaneously)
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The BI G - dif f icult question:
What does it mean “To Understand the brain?”
Clearl y - A THEORY is required to
explains how the brain ingredients
(i ts anatomical units; its electro-chemical signals)
generate “high level” phenomena
(perception, action, emotions) F r
o m m
o l e c u l e
s t o b e h a v i o r
Meters
Centimeters
Millimeter
s
Micrometers
Nanometers
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Recent Brain-Excitements
1. Connectomics – Complete 3D road-map for the brain
2. Brainbow – Colorful, genetically-designed, brains
3. Brain-machine/computer interface (BMI)
4. Optogenetics – Light-activated brain circuits
5. Computer simulation of the brain - Blue Brain Project”
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Modern neuroanatomy
Mapping/visualizing the wiring diagram of the brain
Connecting fine structure to mental activities in healthand in neuro-psychiatric disorders
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Beginning of Modern Neuroscience – Cellular Anatomy
The two giants: Camillo Golgi (Italy) & S. Ramon Y Cajal (Spain) – Nobel Prize 1906
Using Golgi staining method
Very small % of cells stained
Connections (synapses) - not seen
C a m i l l o G o l g i
S
. R a m o n Y C a j a l
The neuron doctrine (Cajal)
Our brain is built from individual cells
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Frontiers 1: Connectomics - modern brain anatomy
Electron microscope (EM) reconstruction of a whole piece of brain (nanometers
resolution). All neurons (and other cell types) and all connections (synapses)
Courtesy of Mitya Chklovskii (Janelia Farm)
Based on hippocampus data from Kristen Harris (U. Texas, Austin)
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Connectomics – complete 3D reconstruction a small volume of
mammalian cortex
Courtesy of Sebastian Seung (MIT)
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Some prospects for the Connectomics
1. We will have, for the first time ever, the “ blue print” (the
anatomical foundation) of a whole (healthy and sick) brain
2. We may start to bridge the “structure-to-function” problem (lecture
#6) and enable realistic computer simulations (“simulation- based”
research) of the respected (healthy or sick) network (lecture #7)
F ti 2 “B i b ” t h l
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Frontiers 2. “Brainbow” technology
Genetic staining of neurons in vivo (light microscope – micrometer resolution)
Courtesy of Jeff Lichtman, Jean Livet and Joshua R. Sanes
Brainbow transgenes drive the combinatorial expression of several fluorescent proteins (XFPs) in
neurons, resulting in the colour-tagging of individual cells.
“ ”
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“Brainbow” images – The colorful brain
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Some prospects for the Brainbow
1. The structural basis for learning in the brain
2. Tagging and genetic-characterization of the different cell-types (the building blocks) in a given system (e.g., retina)
3. Tracing short-and-long range connections in brain circuits
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Frontiers 3. Brain Machine/Computer Interface (BMI)
On-line BMI requires “reading” the electrical activity
( its“electrical language” – its code – lessons #3 & #4 )
in well-defined (functional) regions.
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From Brain to Machine
Spikes in a cell
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Brain-activated robot arm
Courtesy of Miguel Nicolelis (Duke University)
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Courtesy of Andrew Schwartz, Univ. Pittsburgh
Monkey’s brain activity used for self feeding with a robotic arm
From machine (pulses generated by a battery) to brain
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The
Basal
Ganglia
From machine (pulses generated by a battery) to brain
(the amazing success of BMI for ameliorating Parkinosn’s)
Normal
ParkinsonCourtesy of Hagai Berman, Hebrew Univ.
Parkinson
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Implanting stimulating electrodes in patient’s brain (fully alert)
Stimulatingelectrodes
Pulsegenerator
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Deep Brain Stimulation
Patient: Male, 58 years old (PD Eight years, with extreme on-off)
Courtesy of Hagai Bergman, Zvi Israel, Hadassah University Hospital, Jerusalem
(For ameliorating Parkison’s symptoms)
Post-operation Pre-operation
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Courtesy of Miguel Nicolelis (Duke University)
Future challenges for BMI
1. Develop chronic brain nano- probes
2. Develop telemetric communication with the brain
3. Develop real-time multi
(millions?) signal processing
methods
4. Improving robotic arm and
“Closing the loop” Stimulation +
recording
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H a u s s er an d S m
i t h ,N a t ur e2 0 0 7
Frontiers 3: OPTOGENETICSFrontier 4. Optogenetics
Optical stimulation (and recording) from single neurons in the living brain
Channel Rhodopsin opens with blue light
Causes spikes
Natronomonas pharaonis activated with yellow light
Prevents spikes
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Light-activated (~100 neurons) controlling mouse behavior
Courtesy of Karel Svoboda, Janelia Farm
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Frontier 5. Computer simulation of neuronal circuits
Integrating anatomical and physiological data to provide “understanding”
I am never content unti l I have constructed a mathematical model of what I am studying.
I f I succeed in making one, I understand; otherwise I do not ’ William Thomson (Lord Kelvin)
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The Blue Brain Project
Using the powerful “Blue-Gene” IBM Computer for realistic
simulation of the cortical circuits
Courtesy of Henry Markram and the Blue Brain team (EPFL, Switzerland)
Step 1 – Mathematical models of neurons’ spiking activity
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real
model
Step 1 Mathematical models of neurons spiking activity
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Connecting model components (modeled neurons) as in real cortical circuit
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Computer voyage into cortical circuit (the cortical column)
Computer simulation of 10 000 neurons and 100 M
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Computer simulation of 10,000 neurons and 100 M
synapses in 2 cubic mm of cortical circuit
(electrical activity is color coded)
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End of lesson 1
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