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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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Organization of the Brain
Hemispheres
MRI imaging
Regions
PET imaging
Connections
Neurons
Synapses
2-deoxyglucose labelling
Multi-cell recordings
Single-cell recordings
Electrical and chemical events
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Brain
Front
Back
The Central
Nervous
System:
Spinal cord
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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 (19262005), a neurosurgeon.
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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.
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.
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Now the picture of a
spoon is flashed to the
left of the dot.
Language,
Math,
Logic
Spatial abilities,
Face recognition,
Visual imagery,
Music
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
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hemisphere is not stupid, it just has little ability for language - it is "non-verbal."
Functionisisoften
oftenlocalized
localizedtotospecific
specificbrain
brainregions
regions
Function
front
Front
back
Back
acetylcholine
memory
(nicotine)
(hippocampus)
and
dopamine
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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.
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Parts of two neurons
Postsynaptic
neuron
Presynaptic
neuron
Excitatory Inhibitory
terminal terminal
Greek, “axis”
presynaptic
terminal
axon
dendrites
Greek, “tree”
cell
body
nucleus
presynaptic
terminal
postsynaptic
dendrite
synaptic
cleft
direction of information flow
Nestler Figure 2-2
(rotated)
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The synapse is a point of information processing
Greek, “connection, junction”
presynaptic neuron
postsynaptic neuron
Nestler Box 2-3 Figure A
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!
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Chemistry is a language of the nervous system, for instance at synapses
cytosol
synaptic cleft
cytosol
receptor
presynaptic
terminal
postsynaptic
dendrite
receptor
transmitter molecules
receptor
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 electrodes
1. Responses to artificially applied current pulses
http://info.med.yale.edu/neu
robio/mccormick/movies/fs_
ctx1.mpg
V
Same data;
choice of 3 formats.
Media player required
http://info.med.yale.edu/neu
robio/mccormick/movies/fs_
ctx1.avi
http://info.med.yale.edu/ne
urobio/mccormick/movies/f
s_ctx1.mov
(The spikes in these examples are about 100 mV in amplitude)
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Intracellular recording with sharp glass electrodes
2. Artificially applied acetylcholine acts on nicotinic
acetylcholine receptors to produce currents
http://info.med.yale.edu/neu
robio/mccormick/movies/ac
h_fin.mpg
V
Same data;
choice of 3 formats.
Media player required
http://info.med.yale.edu/neu
robio/mccormick/movies/ac
h_fin.avi
http://info.med.yale.edu/neu
robio/mccormick/movies/ac
h_fin.mov
(The spikes in these examples are about 100 mV in amplitude)
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Intracellular recording with sharp glass electrodes
3. A cell is receiving stimuli from other cells, not from the experimenter
http://info.med.yale.edu/ne
urobio/mccormick/movies/rl
y_exp.mpg
V
Same data;
choice of 3 formats.
Media player required
http://info.med.yale.edu/neu
robio/mccormick/movies/rly
_exp.avi
http://info.med.yale.edu/ne
urobio/mccormick/movies/r
ly_exp.mov
(The spikes in these examples are about 100 mV in amplitude)
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2-deoxyglucose can label thousands or millions of active cells at once
cell
activity
glucose
glucose phosphates
metabolic products,
ATP
cell
2-deoxyglucose
(radiolabelled)
activity
2-deoxyglucose phosphates
No metabolic products;
label remains in cell
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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 g 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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A 2-deoxyglucose PET scanning experiment
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
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Nuclear Magnetic Resonance
and
Magnetic Resonance Imaging (MRI)
Nuclei of interest
Proton
Carbon
Sodium
Phosphorus
Xenon
1H
H2O, fat
13C
23Na
31P
ATP, ADP, Phosphate
129Xe
These nuclei possess spin angular momentum (mh/2p)
& thus a magnetic moment (m)
m = I, I-1, …-I 2I+1 values of m
m = gIh/2p
g gyromagnetic ratio
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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)g(h/2p) B0
E(m= - ½) = - (½)g(h/2p) B0
DE = g(h/2p)B0
m = + ½ (antiparallel)
N+1/2
DE
= exp(-DE/kt)
N-1/2
m = - ½ (parallel)
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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DE =g(h/2p)B0 : resonance condition
B0 (tesla)
0.5
1.5
4.7
11.7
n (MHz)
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64
200
500
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
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m precesses in B0
just as a top wobbles in a gravitational field
Intensity
90o B1 pulse
B0
z
Mz
yL
xL
experimental setup
time
The decay characterizes the interactions
with surrounding molecules
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Making a picture from Magnetic Resonance Imaging Data
Front (high freq)
Left
(Phase
advanced)
Right
(Phase
retarded)
Back (low freq)
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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One afternoon’s worth of results:
1. Action Potential
“all or nothing” character of electrical excitation.
2. Rate Code
Increasing stimulus intensity increases discharge frequency
(without affecting the amplitude or duration of individual impulses)
3. Adaptation
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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Population Coding
“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
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Population coding at the 1961 Rose Ball
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voltage
Action Potentials
time
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Extracellular Microelectrode
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Multi-site probe
tetrode
10 μm
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Channel 1
Channel 2
tetrode
Channel 3
Channel 4
Amp. Channel 3
Amp. Channel 4
neuron 2
neuron 1
10 mm
Amp. Channel 2
neuron 2
neuron 1
Amp. Channel 1
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16 site silicon probe
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G. Buzsaki, Neuron, Vol 33, 325-340, 2002
500 μV
100 ms
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Hippocampal Slow-Wave Sleep Recordings
500 μV
100 ms
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500 μV
Hippocampal Ripple
100 ms
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