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Bi 1 Session 4

Monday, April 3, 2006

What is a Brain?

Introduction to neuronal circuits, neurons, synapses, non-invasive imaging, and multi-electrode recording

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Synapses Single-cell recordings

Neurons Multi-cell recordings

Regions PET imaging

Hemispheres MRI imaging

Connections 2-deoxyglucose labelling

Electrical and chemical events

Organization of the Brain

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The Central Nervous System:

Brain

Spinal cord

Front Back

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Function is localized to each hemisphere

Roger Sperry of Caltech (Nobel Prize,1981)

Sperry investigated patients whose corpus callosum had been cut to stop intractable epilepsy. The surgeries were performed by Dr. Joseph Bogen (1926-2005), a neurosurgeon.

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Language,Math,Logic

Spatial abilities,Face recognition,Visual imagery,

Music

The visual information about the spoon crosses via the optic nerve

and travels to the LEFT HEMISPHERE.

The person correctly identifies the spoon verbally.

A split-brain patient fixates on the dot in the middle of a screen. Then a picture of a spoon is flashed to the right of the dot.

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Now the visual information travels to the RIGHT HEMISPHERE. Now if the subject is asked to identify the picture, he reports seeing nothing.

But, when this same subject is asked to pick out an object using only the LEFT hand, he correctly picks out the spoon. This is because touch information from the left hand crosses over to the right hemisphere - the side that "saw" the spoon.

However, if he is again asked to identify the object verbally, even when it is in his hand, he cannot do so because the right hemisphere cannot "talk." So, the right hemisphere is not stupid, it just has little ability for language - it is "non-verbal."

Now the picture of a spoon is flashed to the left of the dot.

Language,Math,Logic

Spatial abilities,Face recognition,Visual imagery,

Music

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Function is often localized to specific brain regions

BackFront

acetylcholine(nicotine)

anddopamine

front back

Function is often localized to specific brain regions

memory(hippocampus)

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A typical pathway: sensation of pain and the reaction to pain

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Spinal reflexes, such as the knee-jerk, involve just two neurons.

sensory neuron

motor neuron

the sensory neuron acts like a strain gauge wrapped around a special muscle fiber.

10Nestler Figure 2-2(rotated)

Parts of two neurons

synaptic cleft

direction of information flow

dendrites

Excitatoryterminal

cell body

nucleus

axon

presynaptic terminal postsynaptic

dendrite

Inhibitoryterminal presynaptic

terminal

neuronPresynaptic

neuronPostsynaptic

Greek, “tree”

Greek, “axis”

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presynaptic neuron postsynaptic neuron

The synapse is a point of information processing

An adult human brain contains ~ 1011 neurons,

and each of these might receive 103 synapses apiece,

for a total of 1014 synapses.

Most of these synapses form during the first 2 yr of life.

Thus 1014synapses/108 s = 106 synapses/s form in a fetus and infant!

Nestler Box 2-3 Figure A

Greek, “connection, junction”

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cytosol

receptor

cytosolsynaptic cleft

transmitter molecules

receptor

receptor

Chemistry is a language of the nervous system, for instance at synapses

presynaptic terminal

postsynaptic dendrite

direction of information flow

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Electricity is a language of the nervous system

Nestler Figure 3-1B

Modified from Nestler Figure 3-1B

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Intracellular recording with sharp glass electrodes1. Responses to artificially applied current pulses

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(The spikes in these examples are about 100 mV in amplitude)

Same data;choice of 3 formats.

Media player required

http://info.med.yale.edu/neurobio/mccormick/movies/fs_ctx1.mpg

http://info.med.yale.edu/neurobio/mccormick/movies/fs_ctx1.avi

http://info.med.yale.edu/neurobio/mccormick/movies/fs_ctx1.mov

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Intracellular recording with sharp glass electrodes2. Artificially applied acetylcholine acts on nicotinic

acetylcholine receptors to produce currents

(The spikes in these examples are about 100 mV in amplitude)

Same data;choice of 3 formats.

Media player required

http://info.med.yale.edu/neurobio/mccormick/movies/ach_fin.mpg

http://info.med.yale.edu/neurobio/mccormick/movies/ach_fin.avi

http://info.med.yale.edu/neurobio/mccormick/movies/ach_fin.mov

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Intracellular recording with sharp glass electrodes3. A cell is receiving stimuli from other cells, not from the experimenter

(The spikes in these examples are about 100 mV in amplitude)

Same data;choice of 3 formats.

Media player required

http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.mpg

http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.mov

http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.avi

V

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2-deoxyglucose(radiolabelled)

glucose glucose phosphates

metabolic products,ATP

cell

2-deoxyglucose phosphates

No metabolic products; label remains in cell

cell

activity

activity

2-deoxyglucose can label thousands or millions of active cells at once

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Positron emission tomography (PET) The probe is [18F]fluoro-2-deoxyglucose. The 18F nucleus decays, eventually yielding a positron which annihilates with an electron to produce a pair of rays (photons). These travel in opposite directions. The two coincident photons intersect an array of detectors. The point of origin is on the line between the two detectors; and “tomography” is the set of algorithms that compute the point of origin from many independent events.

1st nucleus

2nd nucleus

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1. Inject with 5 millicuries of [18F]fluoro-2-deoxyglucose . 2. Repeat a list of 60 common words for ~ 32 min. The “encoding” phase.3. Determine the most metabolically active brain areas. 4. The next day, ask the subjects to recall the words during 5 minutes. The “retrieval” phase.

Alkire et al PNAS (1998) 95, 14506

A 2-deoxyglucose PET scanning experiment

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Nuclei of interest Proton 1H H2O, fatCarbon 13CSodium 23NaPhosphorus 31P ATP, ADP, PhosphateXenon 129Xe

These nuclei possess spin angular momentum (mh/2)

& thus a magnetic moment ()

m = I, I-1, …-I 2I+1 values of m

= Ih/2

gyromagnetic ratio

Nuclear Magnetic Resonanceand

Magnetic Resonance Imaging (MRI)

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In presence of a magnetic field (B0 along lab z-axis )

2I+1 energy levels for the spins (Zeeman levels)

for protons with spin ½ there are 2 Zeeman levels

E(m=+ ½) = +(½)(h/2) B0

E(m= - ½) = - (½)(h/2) B0

E = (h/2)B0

E

m = + ½ (antiparallel)

m = - ½ (parallel)

N+1/2

N-1/2

= exp(-E/kt)

At clinical field strengths (1.5 tesla), for every million spins, there are ~5 more spins aligned with versus against field.

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Deoxyhemoglobin is paramagnetic, a convenient “contrast agent”.

Regions of increased brain activity increase oxygen use.

Unknown mechanisms: during locally decreased blood oxygenation, the brain locally increases blood flow!

This leads to “functional MRI”, fMRI

B0 (tesla) (MHz) 0.5 21 1.5 64 4.7 200 11.7 500

E =(h/2)B0 : resonance condition

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yL

xL

z

Mz

experimental setup

time

Inte

nsity

90o B1 pulse

The decay characterizes the interactions with surrounding molecules

B0

precesses in B0

just as a top wobbles in a gravitational field

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Back (low freq)

Front (high freq)

Left (Phase

advanced)

Right (Phase

retarded)

Making a picture from Magnetic Resonance Imaging Data

Composite

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An fMRI Investigation of Emotional Engagement in Moral Judgment

The experimenters used a battery of 60 practical

dilemmas. These dilemmas were divided into "moral"

and "non-moral" categories on the basis of the responses

of pilot participants. Example of “moral” dilemma: stop a

runaway train by pushing a person onto the tracks.

Specific regions,

Which also participate in emotion, show

activity.

Greene et al (2001) Science 293, 2105

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The first image of brain function

Caltech - Huntington Hospital Proton MRI for structure Phosphorus MRI for function

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Cameo by Professor Thanos Siapas:

multitetrode recording

http://www.search.caltech.edu/CIT_People/action.lasso?-Professor Thanos Siapas&-response=Detail_Person.html&-

layout=all_fields&person_id=50723&-search

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To save file space, the historical slides have been moved to another, optional file:

http://www.its.caltech.edu/~lester/Bi-1-2006/Lecture-images/Lecture-4-2006(History).ppt

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1. Action Potential

2. Rate Code

3. Adaptation

One afternoon’s worth of results:

“all or nothing” character of electrical excitation.

Increasing stimulus intensity increases discharge frequency (without affecting the amplitude or duration of individual impulses)

Neurons respond to changes in their inputs and quiet down at steady state.The brain is interested in changes, not steady state.

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“Within the central nervous system the events in each unit are not so important. We are more concerned with the inter-actions of large numbers, and our problem is to find the way in which such interactions can take place.”

E.D. Adrian, 1932

Population Coding

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Population coding at the 1961 Rose Ball

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Action Potentials

time

volta

ge

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Extracellular Microelectrode

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10 μm

tetrode

Multi-site probe

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Am

p. C

han

nel

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Amp. Channel 210 m

Am

p. C

han

nel

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Amp. Channel 1

neuron 2

neuron 1

neuron 2neuron 1

Channel 2

Channel 1

Channel 3

Channel 4

tetr

od

e

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16 site silicon probe

G. Buzsaki, Neuron, Vol 33, 325-340, 2002

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500 μV

100 ms

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500

μV100 ms

Hippocampal Slow-Wave Sleep Recordings

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500

μV

100 ms

Hippocampal Ripple

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