Physiological Basis of Behavior
jp-rosenfeld@northwestern.edu
We study how the brain
makes mind and behavior
METHODS (in oversimplification terms):
1.Lesions (Ablation): Oldest Method; 2 ways:
a) Natural: Take them as they come (bullet
holes, tumors; “Neuropsychology”.)
b) You do it: chemicals, electricity (cheap).
2. Stimulation: “the opposite of lesions.”
Again, electrical or chemical.
3. Recording: a)Imaging (PET, fMRI),
b)Electrophysiology (EEG, ERP from neuron
populations, or from single neurons)
Lesions and Stimulation…
 ….. Assume that single structures are
responsible for single behavior patterns or
psychological functions. This is the height
of naiveté, to wit……...
“Structure A is substrate for anger.” Ergo…
 a) If you lesion it, no more anger, as in
lobotomy. (Usually no more lots of other
stuff too.)
 b) If you stimulate it, you get a guy angry..
Jose Delgado did the reverse…..
http://www.youtube.com/watch?v=6nGAr2Ok
VqE
Brain and CNS are made
of cells:
Neurons
 Of course, real neurons come in all
shapes & sizes, like the following:
 Drawing by Santiago Ramón y Cajal of neurons in the
pigeon cerebellum. (A) Denotes Purkinje cells, an
example of a multipolar neuron. (B) Denotes granule
cells which are also multipolar.
A) Purkinje Cells, B) Granule
Cells
Or…….
http://www.youtube.com/watch?v
=ifD1YG07fB8&feature=related
 The job of the nervous system
is to transmit information from
neuron to neuron, and to a
target organ like a muscle
which initiates behavior.
As we were saying…
 The job of the nervous system is to
transmit information from neuron to
neuron, and to a target organ like a
muscle which initiates behavior.
 This happens by action potential
(“spike”) propagation down a neuron,
and, usually, via synaptic transmission
to another neuron.
What’s a “potential?”
 The name implies the ability to
do work…electrical work, the
ability to move charged
particles from one level of
potential to another, lower
level.
All cells have a resting
potential.
 That is, a relatively constant
difference in electrical potential
across the cell membrane. Say
+30 mV inside vs. – 10 mv outside.
 This is where they spend most of
their lives…at rest..it’s a good life.
 “Irritable” tissue—muscle cells or
nerve cells--- are different
Irritable cells…..
 …..occasionally show sudden fast
changes in cell membrane
potential, before recovering the
resting level.
 In neurons, these changes are
called “impulses” or action
potentials, and they propagate
from cell body to end of neuron.
Here is a neuron membrane
passing from rest to action
and back to rest…
In the next lecture or
two….
 ….we will consider how the
resting neuronal membrane
potential and the action potential
are generated.
 To do this, we need to do some
thought experiments…
OK, first, let us note that there are 3
passive phenomena mainly influencing
the situation within a neuron:
 (Passive means life is irrelevant to
these phenomena.)
1. Membrane (semi-) permeability.
2. Chemical or concentration forces:
Particles tend to move away from high
and to low concentration.
3. Electrical forces. + “likes” – and
“dislikes” +. – “likes” + and “dislikes” –
OK, now, back to those thought
experiments……
Consider a beaker of water divided by a
semi-permeable membrane into 2
compartments, and I put a teaspoon of
a monovalent salt into the left
compartment. What does the salt ”want
to” do? What forces are at work?
OK, the concentration forces drive ions
to the right. No problem, both positive
and negative ions can go through, so do.
Now what forces act?
..So another pair go through, which puts
system at balance or electrochemical
equillibrium…with no difference in
potential(=voltage)across the membrane
OK, here’s a new situation. What’s
different? What forces?
OK, only the cation can get through in
the first instant. It does. Let’s now
analyze forces and predict next
moment.
The anion “wants to” follow the cation
but is too big. (Good example of
semipermeability.) What are forces
now , and can we predict next moment?
We now have electrochemical
equilibrium (There is still Fc but
balanced by Fe) but with a residual
voltage across the membrane
In the previous slide, the one permeable
little cation is said to be:
at its Equilibrium Potential.
 This is the voltage across the
membrane at which the electrical
and chemical forces on the ion are
in balance.
 Fc + Fe = 0 or
 Fe = -Fc
The situation (figure) in a resting
neuron is more complicated: Given
this situation what are forces on K+,
the most permeable cation?
More complicated because more ions
are involved, and they together affect
electrical and chemical forces.
You should note that there is
a relationship between Fc
and Fe…
 …i.e., the dis-proportionality
between the left and right hand
concentrations of permeable ions
predicts the voltage across
membrane at which system is at
equilibrium. Thus we have an
equation, the Nernst equation, which
holds if K+ is sole permeable ion:
 NERNST EQUATION: E =60 Log (K+o/K+i)
NERNST EQUATION with GOLDMAN
EXTENTION : Derivation:
 Total Force on an ion, say K+ = Electrical Force +
Concentration (Chemical) Force.
 Putting in units of Voltage, the total electrochemical force =
 DV[K+] = ZFE + RT ln (K+i/K+o)
 (Z= charge/mole,F= valence,E=membrance potential in
voltage units, R= gas constant, T= temperature(absolute), ln =
log to base e, K+i = inside Potassium concentration, K +o =
outside Pot. Conc.)
 When K+ is at electrochemical equilibrium, DV[K+] = 0 = C1E +
C2 ln (Ki+ /K+o), where C1,C2….(all C) are constants.
 So
 C1E = - C2 ln (K+i/K+o) = C3 ln (K+o/K+i), and dividing both sides
by C1 yields
 E=C3/C1 ln (K+o/K+i) = C4 ln (K+o/K+i) =C5 log10 (K+o/ K+i ). C5=
about 60, so
 NERNST EQUATION: E =60 Log (K+o/K+i) [Note: Log (x) = Log to
base 10]
It is noted that this applies when
only permeable ion is K+
 . Otherwise, one uses the Goldman equation (of which
the Nernst is seen to be a special case).
 E= 60 Log (PK [Ko+] + PNa [Nao+]+Pcl [Cli-]…….)/
 (Pk [Ki +] PNa [Nai +] + Pcl [Clo-]…….)
 Pk= potassium permeability coefficient, Pna= perm
coeff for Na, Pcl= perm coeff for Cl. Signs of ions
omitted for clarity, but note, cation outside
concentrations are in numerators, anion outside
concentrations in denominator. Note what happens to
equation if all coefficients but Pk go to zero.
 Sample question: If K+o = 10000 and K+i =10, what is E if
K+ is sole permeable ion? In other words, what is the K+
equilibrium potential?
This Nernst Equation….
 Allows us to see if a neuron is
near/at equilibrium and if that ion
is sole permeable one.
 Thus if we calculate the
equilibrium potential for K+, we
use: E = 60 log ([K+]0/[K+]i) = -80
which is close to but not = to the
actual -70. Meaning…?
The Equilibrium Potential of Na+..
 Using the concentrations of Na+ inside and
outside in the equation yields the
equilibrium potential for Na+:
 E = 60 log ([Na+]0/[Na+]i) =
+65 mV
…but the real resting membrane potential is
-70mV
Is Na+ at equilibrium? We already guessed
that it wasn’t due to Fc and Fe. What do we
conclude about PNa or Na+ permeability?
Back to the neuron…
Thus, the resting membrane potential is
there because relatively permeable K+
moves as close to equilibrium as it can…
 Is there proof? Yes. Scientists have
manipulated interior and exterior
[K+] and noted the effect on Em, the
membrane resting pot.
 They manipulate exterior [K+] simply
by bathing neurons in solutions
where [K+] systematically varies.
Interior [K+] is manipulated as if
neuron were a toothpaste tube.
Both can be simultaneously
changed.
Here are the results…
Why the discrepancy??
1) 90% is due to presence and
influence of other ions. So if you
used Goldman extension, most of
discrepancy would go away:
E= 60 Log (PK [Ko+] + PNa [Nao+]+Pcl [Cli-]…….)/
(Pk [Ki +] PNa [Nai +] + Pcl [Clo-]…….)
= ~ -79 mV
The rest of the discrepancyis
due to the… 2)
Na+ & K+ Ion exchange mechanism,
Or the “Sodium Pump.”
This is a dynamic biochemical
process that keeps Na+ out and
K+ in, as the video will now
demonstrate…..
http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/a
nimation__how_the_sodium_potassium_pump_works.
html
The whole story
 http://www.google.com/#q=hodgkin+experiment&hl=
en&prmd=iv&source=lnms&tbs=vid:1&ei=kTyeTL2xKY
KWnAftvinDQ&sa=X&oi=mode_link&ct=mode&sqi=2&ved=0C
AgQ_AU&fp=8a8ae2f39e51403c
Measuring Neuronal Voltages
Better for fast things (spikes)….
Hodgkin Experiment
One stimulation of + 10 mV,
a depolarization…
You always see the
overshoot…
…until you see
the action
potential!
4 stimulations….. (Bucking Currents)
Voltage Gated Ion Channels.
 The first channels to open are Na+
channels.
 The first critical finding by
Hodgkin was that the greater the
depolarization across the
membrane, the greater the Na+
permeability (PNa), so Na+ rushes
in (why?) which further
depolarizes membrane.
Hodgkin Cycle (inner
wheel)
Why doesn’t it inevitably lead to
a spike?
 Because although the first effect
of depolarization in opens Na+
channels so Na+ rushes in….
 There is a delayed effect of the
stimulation/depolarization, which
is to more slowly open K+
channels. What does K+ “want to”
do?
Inner wheel PLUS Outer wheel
The outer wheel …
 ….puts the brakes on the inner
wheel. Whether you get a
spike or re-polarization
depends on the race between
the inner and outer wheels.
See James Stewart version of
“Flight of the Phoenix.”
 http://www.youtube.com/watch?v=XYUnEOxU2LE&f
eature=related
Theory of the Action
potential--Hodgkin
http://www.afodor.net/HHModel.h
tm
Evidence:
1. The spike top = ~ +60 mV which
is close to the equilibrium
potential for Na+.
2. The spike top can be
manipulated:
…as in these experiments.
Well this is nice…
 But this evidence is about one
instant in time—the peak of the
spike, but…..
Hodgkin model is about the whole
epoch: from resting potential to
spike top, and back to baseline, and
concerns in and out ionic
movements, Na+ in and K+ out later,
and causal permeability changes.
In other words…
 The Hodgkin model is dynamic
concerning changes during time.
 For this, one needs special
methods, the voltage clamp or
current injector.
Remember this?
Let’s add superscientist who monitors
scope and injects equal & opposing
current:This clamps voltage.
Superscientists don’t exist…but Analog
amplifiers do……
In other words…
Even during a naturally
occurring spike, the clamp
keeps voltage constant by
injecting ions as necessary.
An Experiment with a voltage clamp
or current injector
This PROVES even the dynamic
parts of Hodgkin-Huxley Model:
 During the action potential, there
is an early inward flow which is
Na+ rushing in.
 ….and a delayed outward flow
which is K+ leaking back out and
helping to restore resting
potantial, aided by NA-K pump.
Kymograph: NM preparation
By the way…..
 A Nerve is a bundle of axons…
Old Principles (from 1930s)
explained:
The Kymograph told us of
“All or none” means either you got the
whole spike (-70 to +60= 130) or
none. All because Na+ goes to its
equilibrium potential.
“Refractory periods” harder to
activate neuron = Na+ conductance
inactivated.
“Threshold”= when Inner wheel
outruns outer wheel & brakes fail.
The spike propagates undiminished
(all or none) to end. How?
What if you stimulate axon in
middle?
 You get propagation in both
directions.
 Orthodromic (natural) vs.
Antidromic (experimental)
conduction. To test where a cell
body of a long axon is.
Determinants of Conduction
Speed
 Physical: temperature, diameter.
 Physiological: Nodes, Myelin.
 Continuous vs Saltatory
Conduction
Continuous vs Saltatory
Conduction
Strength-Duration Curve
What happens if you
depolarize, but don’t get a
spike? You get:
Cable properties: decay over
time and distance.
If you looked 3 times at one
place:
Why does it decay without a spike?
And why doesn’t spike?
Here’s a resting axon:
We introduce a sub threshold
stimulation. What happens?
The positivity put in repels other
positives up to membrane, which causes
outside +’s to be repelled—Capacitative
current.
Capacitative flow means no
actual physical movement..
Pretty soon, the inside of the
membrane would have a full
capacity of + charge.
Meanwhile, more + charge has
accumulated further down and
acts like a depolarizer..BUT..
Meanwhile….
So the membrane has capacitance
& resistance, as does the
axoplasm..and we can represent
membrane like this…
Why is a spike undiminished and
propagated?
 Because the initial and each
subsequent change in potential is
all the way to the Na+ equilibrium
potential. Enough na+ rushes in at
each segment to FULLY depolarize
(to +60) the next segment.
In living mammals, the usual
way of activating a neuron…
 ….is not with stimulators
causing threshold or subthreshold polarizations.
 It is with :
Synaptic Transmission
Some notes:
 Presynaptic terminals are boutons de
terminaux or terminal buttons.
Post synaptic structures are usually
either the dendritic branches
(“arborizations”) or the cell body itself.
Pre synaptic spikes lead to release & flow
of transmitter from terminals. There is
both excitatory and inhibitory
transmitter making depos & hyperpos,
respectively, (EPSP, IPSP), at
postsynaptic neurons.
Postsynaptic EPSP and IPSP:
Types of synapses:
There is also ephaptic transmission,
direct electrical activation of one
neuron by another…
 These are called “tight junctions,”
(or “gap junctions”) as they are
only 40Ao apart. Ephapses that
make spikes are mostly in
invertebrates.
 But there are sub-threshold
ephaptic influences in mammals.
Better diagram of A-D, A-S
Axosomatic micrographs
Properties of synaptic information
transmission (contrasted with spike
propagation down axon):
 1. S.T. is unidirectional in CNS because
transmitter is presynaptic. (In axons, you can
have ortho & antidromic, i.e., bi-directional
information flow.)
 2. You can have repetitive discharge in S.T.
With presy stim., big flow of (pre-sy)
transmitter can fire the post-synaptic cell
repeatedly. (Unlike 1:1 spike on axon)
 3. Related, in S.T.,there is not necessarily
“frequency following.” (Yes on axon, if you
stimulate the axon and record from axon.)
More properties of synaptic
information transmission
(contrasted with spike propagation
down axon):
 4. Synapses have low safety factor.
Means likely loss of information due
to susceptibility to drop in 02
concentration, drugs, etc. in synapse
(vs. axon).
 5.Reasons for delay in information
flow. In S.T. it is number of synapses.
(In axon, it’s diameter,
presence(absence) of myelin.)
More properties of synaptic
information transmission
(contrasted with spike propagation
down axon):
 6. There can be either Inhibition or
Excitation at synapse. (Only
excitation for spike flow. All or
none.)
 7. Synaptic potentials are
graded/additive. (Only all or none
spike.)
 8. Synaptic potentials are local
like sub-threshold depos. (Spikes
propagate undiminished.)
7. & 8. have major implication:
 There is no such thing as a unitary
 EPSP (or IPSP). You may hear a
phrase like “the EPSP” (or “the
IPSP”) but the size of EPSP or
IPSP depends on amount of
excitatory or inhibitory
transmitter simultaneously
reaching post synaptic membrane.
This was most persuasively shown..
 …by the great Australian
neurophysiologist, Sir John
Eccles of Canberra (later
Buffalo).
Eccles’ classic demonstrations
of Spatial Summation:
Temporal Summation
So he actually
demonstrated that…..
 …the EPSP size depends on the
temporally and spatially
integrated positive (EPSP,
depolarizing) and negative (IPSP,
hyperpolarizing) input.
Same is true of IPSP….
Eccles did another brilliant
demonstration:
There was more: The second
hump= spike could be further
“dissected”:
The inflection points (when
2nd derivative =0) required
use of analog computers.
 The Initial Segment of the axon, also
called the axon hillock, has a lower
threshold than the rest of the axon,
and it is a relay booster when
necessary, which is good for safety
factor.
 There is electron microscopic
evidence that I.S. membrane has
different structure (slightly) than
main axon membrane.
Mechanisms of PSPs:
 EPSP: Excitatory transmitter
increases both Na+ and K+
permeabilities. It has an
“equilibrium potential” ~ 0. This is,
of course, a depolarization. Tends
to cause a spike if big and
widespread enough.
Mechanisms of PSPs:
 IPSP: involves increase in
permeability to CL- and especially,
K+. It has an “equilibrium
potential” ~ -89, which is
hyperpolarizing away from -70.
This puts the neuron away from
 -70, and harder to excite than
when at rest = inhibition.
The “dynamic duo from Deutchland”:
Westecker & Deeke
This was the inference implied by
reduced EPSP, but has since been
confirmed with release experiments.
 That is, they do the D&W clamp
manipulation and look not only at
EPSP size, but actual amount of
transmitter released into synapse.
Note…
 This clamp, at a more positive
voltage level, is not really an
excitatory process, though it
does move neuron in
depolarizing direction. The
voltage is clamped, after all.
Why is this
important? Is
there a parallel
in nature?
What were those
axo-axonic
synapses all
about?
But in nature, we have no voltage
clamps, but we do have axoaxonic
synapses:
Note again….
 On the axon, this is not a true
excitatory process, since it
will never lead to axon spike;
it’s like a chemically mediated,
clamp. The spike is generated
earlier, at green arrow.
Whither all-or none?
 Is this a violation of all or none?—the
fact that base-to-peak spike size may
be reduced?
 Not really. The spike still goes to the
Na+ equilibrium potential, +66. That is
the constant “all” of all or none. We
now just learn that peak is constant,
not necessarily base-peak.
 Is there a parallel pre-synaptic
excitation?
Pre-synaptic Excitation:
Synaptic Transmission is
Chemical. Evidence:
1) LOGICAL/INDIRECT:
a) 2 kinds of PSPs exist and can
be explained by 2 kinds of
chemical transmitters. (Only 1
kind of pre-synaptic spike.)
b) Delay in pathways are
consistent with diffusion times,
not with electrical
conduction=186,000 mps.
LOGICAL/INDIRECT: (Cont.)
c) Post synaptic membrane is not
electrically excitable, which axon
is, but axon is not chemically
excitable (except at axo-axonal
synapses).
Direct Evidence: Loewi’s
Experiment
OK, so what are the chemicals
which are transmitters and where in
CNS are they? McLennan’s 5 criteria
 The 5 criteria a candidate chemical
must meet to be dubbed a
transmitter were developed to
parallel the processes that happen
in synaptic transmission:
1. The first thing to happen is the
synthesis of the transmitter in
presynaptic neuron. Therefore,
McLennan #1 is that presynaptic
terminals should contain precursors
and enzymes of biosynthesis.
Next….
2. After transmitter is made is must
be mobilized (by spike)and diffuse
into synapse. So McLennan # 2 is
that presynaptic spikes must be
followed by release of substance.
3. Then there is a chemical reaction
with neurotransmitter receptor,
leading to a PSP. So McLennan # 3 is
that topical application of substance
must produce PSP. The PSP now
does its job: ex or inh.
Now….
4) The transmitter has arrived at the
post synaptic side and must be
degraded back to its precursors, so
McLennan #4 is that the enzymes of
degradation must be found in the
post-synaptic cell.
…By the way, for some transmitters,
much of what is released is reabsorbed by presynaptic cell, so
never gets there (across cleft) for
degradation…
The last criterion
5. McLennan #5: Consistent in vivo/in
vitro effects, meaning if a substance
is known in the test tube to block a
process—like synthesis of Ach– then
it must be shown to block
Cholinergic processes in behaving
animals. Example: The following
reaction works if Choline Acetylase
is active.
Acetic Acid +Choline ---- ACH
By the way….
 Most candidate neurotransmitters
have not met all 5 criteria and are
therefore called “putative”
neurotransmitters.
 Next we will talk about those that
are pretty well established. These
tend to be in the peripheral N.S.
because that’s where it was easiest
to dissect pathways. Things are
tougher in the brain.
1. Cholinergics: Ach.
Where is Ach found?
 1. Neuromuscular junction (ala
Loewi’s “Vagusstoffe”)
 2. Specific loci in Autonomic
Nervous System (ANS). (later)
 3. Nucleus Basalis: Alzheimers?
 4. Pontine nuclei regulating sleep.
 5. Cerebral Cortex—putative.
Carlson’s adrenergic pathways (The
point of this slide is to show there are
many ACH paths in brain.)
2. Catecholamines: a)Epinephrine
(adrenalin), b)Norepinephrine
(noradrenaline), c)Dopamine. Mixtures of
a+b used to be called “Sympathin.”
Norepinephine
 We will see it is found all over brain
so has many roles in psychological
processes, especially motivation,
reinforcement, emotion.
 Specifically: 1. post-ganglionic
terminals in Sympathetic N.S. and
released from adrenal gland where it
can act everywhere (“fight or
flight.”)
Norepinephine (cont.; The point of this
slide is to show there are many ACH
paths in brain.)
2. Dorsal ascending noradrenergic
tract.
3. Ventral ascending noradrenergic
tract.
These tracts connect pontine
nuclei of origin to virtually the
whole forebrain
Carlson’s version (Doesn’t show
the true origin of VANB!!)
Dopamine: 1. Afferent collaterals
to reticular formation
Dopamine 2. Nigro-Striate Path
Indolamines a) Serotonin or 5hydroxy Tryptamine (5-HT). Found:
 1. Descending raphe-spinal fibers
going from nucleus raphe magnus
in medulla to spinal cord.
Inhibitory.
 2.Other places I leave to your
reading…
The Raphe-Spinal System of
analgesia
By the way, both catecholamines
and indolamines are
 Monamines
Inhibitory amino acid Transmitters:
 GABA (Pretty exclusively
inhibitory.)
 GLYCINE ( +/-)
 GLUTAMATE (+/-)
Everywhere in mammals.
For example, remember this?
There are many other substances
with varying “degrees of putativity.”
 Such as the peptide
neuromodulators*, Enkephalins
and Endorphins (synthetic
opiates),
 Substance “P”
 Nitric Acid (NO)
* These mediate synaptic
transmission but not restricted to
cleft.
OK, so what are some drugs
whose effects are mediated at
synapses or axons? (A Minicourse in Psychopharmacology)
Check web site.
Brief Neuroanatomy. (Good idea to
study each day’s lecture each day)
NOTE:
 I will have the opportunity to
sneak in an introduction to the
topic of neural coding here and
there.
It’s a bit more elaborate.. One
needs to fill in details of “CNS”
By evolution-driven organization..
 …we mean that the higher the
animal, the greater the degree of
encephalization: Sharks get only
up to pons, fish up to midbrain,
some reptiles have a tiny cortex
with few myelinated fibers. This is
also true for the inside out
organization…see next slide:
BrainStem inside-out
organization…
Cortical projection systems
Early specific and late reticular
evoked eeg potentials or event related potentials,
which you get in response to any sensory stimulus—
like that fingertip tap…
Cortical Reticular Arousal :
stimulate r.f. or any sensory path
This change from synchronous (rhythmic)
high amplitude, low frequency to
arhythmic, low amplitude, high frequency
is alpha blocking (or arousal of EEG)
Slightly more realistic….
Other stuff & illustrative
perspective:
Side View of Brainstem with
Cerebellum
Brain Stem Auxilliary( NO= not to
memorize)
Visual System NO
Another view (NO)
My way
Different view
Auditory pathways
NO
Acoustic receptor cartoon (no)
Somatic Sensation
1)Conscious Proprioception
(aka dorsal or posterior column system)
2) Unconscious Proprioception
(cerebellar—we’ll talk about later)
3) Pain & Itch
a) below the neck
b) above the neck
NOTE:
 Here’s where I will also sneak in
an introduction to the topic of
neural coding along the way.
 Neural Coding means how the CNS
represents sensory, motor, and
psychological processes in any
CNS activity: spike pattern, rate;
brain wave frequencies, and
derivatives (more later).
Dorsal (posterior)Column Sense
NO
Neural coding:
 Mountcastle & associates showed
that the firing rate of joint angle
receptors is a logarithmic or
power function of the joint angle
and the speed of rotation to it:
 (These experiments were done on
anaesthtized, sometimes
curarized, always restrained cats
& monkeys.)
The question was: What part(s) of this
complex system mediates facial pain?
Top (main, oralis) or
bottom(caudalis) middle
(interpolaris) or all or two
of the above?
We are sneaking also here
into parallel topic of neural
(sensory) coding
The predominant view:
submodality segregation as in
spinal cord
 Pain caudally (s. caudalis) and nonpain rostrally (main, oralis).
 (In cord, pain is in spinothalamic
tract, ventral, and non-pain is in
dorsal column.)
 This is a labelled line code: place
signals sensation/perception.
 Clinical (surgical) evidence was
supportive: caudal tractotomy
relieved facial pain as in Tic
Doloreaux (trigeminal neuralgia).
But it should have been obvious
that saggital knife cuts in TT would
likely cut the nucleus,rostrally
There was also a “within-line code”
suggested by Khayyatt experiment.
First accidentally motivated study:
 What is the effect of pure
trigeminal nuclear lesions of
rostral subnuclei (main, oralis) on
orofacial pain?
 Motivated by our accidental
finding that stimulation rostrally
was very aversive.
 If stimulation activates pain, then
lesions should remove pain.
How to measure facial pain in a rat?
Face rub latency, inversely.
Knife cut experiment:
How to measure non-pain stimulation
of face? Remember this?
Tested sites on the face:
Facial Pain Results:
Non-painful facial stimulation
results:
So we turned the Dubner
hypothesis upside down…
 In the rat, the top is for pain and
the bottom is for non pain.
 Vyklyky in Czeckoslavakia found
similar result in cat: Lesions of
caudalis did NOT prevent aversive
conditioning with tooth pulp
stimulus! (“Rosenfeld, Ha! Now
there are two of us!”)
Evidence for conscious and
unconscious proprioception:
 1. Spinocerebellar fibers go to
cerebellum, not cortex—the
substrate for consciousness.
Unfortunately, evidence to
contrary was found in ‘63.
2. Better Evidence:
Coolest Evidence:
Cortex
Transition……
 We are now entering the topic of
neural coding formally. How does
CNS activity encode sensory, motor,
and Psychological (cognitive,
emotional, perceptual etc) events?
First we need to examine what the
CNS events are, and that requires us
to go to the next powerpoint on the
web site:
 “EEG,ERPs, & relation to single
neuronal activity.”