Psychology 312-1 Physiological Basis of Behavior

jp-rosenfeld@northwestern.edu

We study how the brain makes mind and behaviorMETHODS (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=6nGAr2OkVqE

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 orFe = -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.mcgraw-hill.com/sites/0072495855/student_view0/

chapter2/

animation__how_the_sodium_potassium_pump_works.html

The whole storyhttp://www.google.com/

#q=hodgkin+experiment&hl=en&prmd=iv&source=lnms&tbs=vid:1&ei=kTyeTL2xKYKWnAftv-inDQ&sa=X&oi=mode_link&ct=mode&sqi=2&ved=0CAgQ_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&feature=related

Theory of the Action potential--Hodgkin

http://www.afodor.net/HHModel.htm

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.

Strength-Duration Curve