Synapses, neurons and brains

Idan Segev

Lesson #1
Brain excitements for the 21st century
 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
 "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 vast assembly
of nerve cells and their associated
molecules"
(Francis Crick, Nobel Laureate 1962 the
father of DNA).

"Machine think? You bet! Were machines and we

think, dont we?"
(Claude Shannon the father of information age)
 The most incomprehensible thing about the world
is that it is at all comprehensible.

So what is the route to comprehend the brain?

 The start

Or

3.5 Billion years of life on earth

The Homo sapiens sapiens

&
The ~ 100 years old Human Brain Project
 3.5
300
500 Million Billion
Million
years
200 Millionyears
years
years
200,000
70 Million
years
years
Fish Life begins - Bacteria
Reptiles
Mammals
Humans
Primates
The development of mammalian big brains
200 Million years - TODAY
 Modern Humans ~ 200,000 years & Cultural Evolution
1500 Understanding/rep
airingourbrain
1400 Today

1300

Culturalevolution
CellPhones,ICT

Brain weight - gr
1200 Today

Brainweight(gr)
1100
ModernComputers
70years
1000

900 Science
3,000years
800
1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0
Million years Millions Language/Math
Millionsofyearsago 5,000years

CultureexplosionofHomosapienssapiens
Art
(60,00030,000ago)
1. Brain Blossom Worldwide

The Jerusalem Brain

(Norman Foster)
A view from the inside (of the brain)
 Structure of modern brain centers & central role of theory
(+ new curriculum for Leonardo da Vinci brain-researchers)

Neuroscience of
Neurological & cognitive
Disorders

Human
Human&&Primate
Primate
Behavior
Behavior andCognition
and Cognition

Plasticity
Plasticity&&Developmental
Developmental
Neuroscience
Neuroscience
Computational
Computational
&&
theoretical
theoretical
Quantitative
QuantitativeAnalysis
Analysis Neuroscience
Neuroscience
of Neuronal circuits
of Neuronal circuits
The da Vinci generation of brain researchers

New Approach: Theory-Driven Brain Research

Neurobiology &
Psychology
Medicine

Theory/Modeling Computer Science

Applied Physics & Engineering

Perspective:Somenewdramatic($billions)projectsforthebrain

1.AllenInstituteSeatle,USA(Mouse/Humanbrainatlasrecentlynew
focusonmousevision)

2.JaneliafarmDC,USA(IndustrialscaleInst.forconnectingnetwork
levelanatomyandphysiologytosspecificbehavior)

3.EUHumanBrainProjectEPFL,LausanneSwitzerland(ICTbasedbrain
researchplatform,integratingdataandknowledgefromdifferentdisciplines,
andcatalyzingworldwideefforttoachieveunderstandingofthebrain,
proposenewtreatmentsforbraindiseasesandnewbrainlikecomputing
technologies)Lesson#7.

4.PresidentObamasBrainActivityMapinitiative(Creatingrevolutionary
toolstomeasure/stimulatemillionsorevenbillionsorneurons
simultaneously)
 Spatial scale

The BIG - difficult question: Meters

What does it mean To Understand the brain?

From molecules to behavior

Centimeters

Clearly - A THEORY is required to

explains how the brain ingredients Millimeters

(its anatomical units; its electro-chemical signals)

generate high level phenomena
Micrometers
(perception, action, emotions)

Nanometers
 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
 Modern neuroanatomy
Mapping/visualizing the wiring diagram of the brain

Connecting fine structure to mental activities in health

and in neuro-psychiatric disorders
 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

S. Ramon Y Cajal
Camillo Golgi

Connections (synapses) - not seen

The neuron doctrine (Cajal)

Our brain is built from individual cells
 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)
Connectomics complete 3D reconstruction a small volume of
mammalian cortex

Courtesy of Sebastian Seung (MIT)

 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)
 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.

Brainbow-1: stochastic recombination using incompatible lox variants.

Brainbow images The colorful brain
 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
Frontiers 3. Brain Machine/Computer Interface (BMI)

On-line BMI requires reading the electrical activity

(itselectrical language its code lessons #3 & #4)
in well-defined (functional) regions.
From Brain to Machine

Spikes in a cell
 Brainactivatedrobotarm

CourtesyofMiguelNicolelis(DukeUniversity)
Monkeys brain activity used for self feeding with a robotic arm

Courtesy of Andrew Schwartz, Univ. Pittsburgh

Frommachine(pulsesgeneratedbyabattery)tobrain
(theamazingsuccessofBMIforamelioratingParkinosns)

Normal
The
Basal
Ganglia

Parkinson

Parkinson
Courtesy of Hagai Berman, Hebrew Univ.
Implanting stimulating electrodes in patients brain (fully alert)

Stimulating
electrodes

Pulse
generator
 Deep Brain Stimulation
(For ameliorating Parkisons symptoms)

Post-operation Pre-operation

Patient: Male, 58 years old (PD Eight years, with extreme on-off)
Courtesy of Hagai Bergman, Zvi Israel, Hadassah University Hospital, Jerusalem
ture challenges for BMI

1. Developchronicbrainnanoprobes
2.Developtelemetriccommunicationwiththebrain

3.Developrealtimemulti
(millions?)signalprocessing
methods

4.Improvingroboticarmand
ClosingtheloopStimulation+
recording
CourtesyofMiguelNicolelis(DukeUniversity)
 Frontier 4. Optogenetics
Frontiers 3: OPTOGENETICS
Optical stimulation (and recording) from single neurons in the living brain

Channel Rhodopsin opens with blue light Natronomonas pharaonis activated with yellow light
Causes spikes Prevents spikes

Hausser and Smith, Nature 2007

Light-activated (~100 neurons) controlling mouse behavior

CourtesyofKarelSvoboda,JaneliaFarm
 Frontier 5. Computer simulation of neuronal circuits
Integrating anatomical and physiological data to provide understanding

I am never content until I have constructed a mathematical model of what I am studying.

If I succeed in making one, I understand; otherwise I do not William Thomson (Lord Kelvin)
 The Blue Brain Project
Using the powerful Blue-Gene IBM Computer for realistic
simulation of the cortical circuits

CourtesyofHenryMarkramandtheBlueBrainteam(EPFL,Switzerland)
Step1Mathematicalmodelsofneuronsspikingactivity

real

model
Connecting model components (modeled neurons) as in real cortical circuit
Computer voyage into cortical circuit (the cortical column)
Computer simulation of 10,000 neurons and 100 M
synapses in 2 cubic mm of cortical circuit
(electrical activity is color coded)
End of lesson 1