Psychology 312-1
Psychology 312-1 Physiological Basis of
[email protected] 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 naivet, to wit... Structure A is
substrate for anger. Ergoa) 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=6nGAr2OkVqEBrain and CNS are made of
cells: Neurons
Of course, real neurons come in all shapes & sizes, like the
following:
Drawing by Santiago Ramn 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=relatedThe
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 sayingThe 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.
Whats a potential?The name implies the ability to do
workelectrical 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 livesat rest..its a
good life. Irritable tissuemuscle cells or nerve cells--- are
differentIrritable 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 experimentsOK, 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.)Membrane (semi-) permeability. Chemical or
concentration forces: Particles tend to move away from high and to
low concentration.Electrical forces. + likes and dislikes +. likes
+ and dislikes OK, now, back to those thought experimentsConsider 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 equillibriumwith no difference in
potential(=voltage)across the membrane
OK, heres a new situation. Whats different? What forces?
OK, only the cation can get through in the first instant. It
does. Lets 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 = -FcThe 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
Fei.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 mVbut the real
resting membrane potential is -70mV
Is Na+ at equilibrium? We already guessed that it wasnt 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 canIs 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??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=8a8ae2f39e51403cMeasuring
Neuronal Voltages
Better for fast things (spikes).
Hodgkin Experiment
One stimulation of + 10 mV,a depolarization
You always see the overshootuntil 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 doesnt 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:The spike top = ~ +60 mV which is close to the
equilibrium potential for Na+.
The spike top can be manipulated:as in these experiments.
Well this is niceBut this evidence is about one instant in
timethe 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 wordsThe Hodgkin model is dynamic concerning changes
during time.
For this, one needs special methods, the voltage clamp or
current injector.Remember this?
Lets add superscientist who monitors scope and injects equal
& opposing current:This clamps voltage.
Superscientists dont existbut Analog amplifiers do
In other wordsEven 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
