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