Psychology 312-1 - PowerPoint Presentation

Slide1

Psychology 312-1

Physio

logical Basis of Behavior

jp-rosenfeld@northwestern.eduSlide2

This is a psychology course…

…BUT:

in this first quarter, it’s hard to tell, as

we mostly

cover neurophysiology,

neuroanatomy

, and

neuropharmacology

. Be warned!Slide3

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)Slide4

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=6nGAr2OkVqESlide5

Brain and CNS are made of cells: NeuronsSlide6

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

.Slide7

A) Purkinje Cells, B) Granule CellsSlide8

Or…….Slide9

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.Slide10

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.Slide11

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.Slide12

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 differentSlide13

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.Slide14

Here is a neuron membrane passing from rest to action and back to rest…Slide15

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…Slide16

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

.)

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 experiments……Slide17

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?Slide18

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?Slide19

..So another pair go through, which puts system at balance or electrochemical

equillibrium

…with no difference in potential(=voltage)across the membraneSlide20

OK, here’s a new situation. What’s different? What forces?Slide21

OK, only the

cation

can get through in the first instant. It does. Let’s now analyze forces and predict next moment.Slide22

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?Slide23

We now have

electrochemical equilibrium

(There is still

Fc

 but balanced by Fe)

but with a residual voltage across the membraneSlide24

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 = -

FcSlide25

The situation (figure) in a resting neuron is more complicated: Given this situation what are forces on K+, the most permeable

cation

?Slide26

More complicated because more

ions are involved

, and they together affect electrical and chemical forces.Slide27

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

) Slide28

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

(

K

i

+

/

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 log

10

(K

+o

/ K

+i

). C5= about 60, so

NERNST EQUATION: E =60 Log (K

+o

/K

+i

) [Note: Log (x) = Log to base 10] Slide29

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 (P

K

[

K

o

+] +

P

Na

[

Na

o

+]+

P

cl

[

Cl

i

-]…….)/

(

P

k

[

K

i

+]

P

Na

[

Na

i

+] +

P

cl

[

Cl

o

-]…….)

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? Slide30

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…?Slide31

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

P

Na

or Na+ permeability?

Slide32

Back to the neuron…Slide33

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.Slide34

Here are the results…Slide35

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 (P

K

[

K

o

+] +

P

Na

[

Na

o

+]+

P

cl

[

Cl

i

-]…….)/

(

P

k

[

K

i

+]

P

Na

[

Na

i

+] +

P

cl

[

Cl

o

-]…….)

= ~ -79 mV Slide36

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.htmlSlide37

The whole story

http://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=8a8ae2f39e51403cSlide38

Measuring Neuronal VoltagesSlide39

Better for fast things (spikes)….Slide40
Slide41

Hodgkin ExperimentSlide42

One stimulation of + 10 mV,

a depolarization…Slide43

You always see the overshoot…

…until you see the action potential!Slide44

4 stimulations….. (Bucking Currents)Slide45

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 (

P

Na

),

so Na+ rushes in (why?) which further depolarizes membrane.Slide46

Hodgkin Cycle (inner wheel)Slide47

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?Slide48

Inner wheel PLUS Outer wheelSlide49

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.”Slide50

http://www.youtube.com/watch?v=XYUnEOxU2LE&feature=relatedSlide51

Theory of the Action potential--HodgkinSlide52

http://www.afodor.net/HHModel.htmSlide53

Evidence:

The spike top = ~ +60 mV which is close to the equilibrium potential for Na+.

The spike top can be manipulated:Slide54

…as in these experiments.Slide55

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.Slide56

In other words…

The Hodgkin model is dynamic concerning changes during time.

For this, one needs special methods, the

voltage clamp

or current injector.Slide57

Remember this?Slide58

Let’s add superscientist

who monitors scope and injects equal & opposing

current:This

clamps voltage.Slide59

Superscientists don’t exist…but Analog amplifiers do……Slide60

In other words…

Even during a naturally occurring spike, the clamp keeps voltage constant by injecting ions as necessary.Slide61

An Experiment with a voltage clamp or current injectorSlide62

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.Slide63

Kymograph: NM preparationSlide64

By the way…..

A Nerve is a bundle of axons…Slide65

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.Slide66
Slide67

The spike propagates undiminished (all or none) to end. How?Slide68

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.Slide69

Determinants of Conduction Speed

Physical: temperature, diameter.

Physiological: Nodes, Myelin.

Continuous

vs

Saltatory

ConductionSlide70

Continuous

vs

Saltatory

ConductionSlide71

Strength-Duration Curve Slide72

What happens if you depolarize, but don’t get a spike? You get:Slide73

Cable properties: decay over time and distance.Slide74

If you looked 3 times at one place:Slide75

Why does it decay without a spike? And why doesn’t spike?

Here’s a resting axon:Slide76

We introduce a

sub threshold

stimulation. What happens?Slide77

The positivity put in repels other positives up to membrane, which causes outside +’s to be repelled—

Capacitative

current.Slide78

Capacitative

flow means no actual physical movement..Slide79

Pretty soon, the inside of the membrane would have a full capacity of + charge.Slide80

Meanwhile, more + charge has accumulated further down and acts like a depolarizer..BUT..Slide81

Meanwhile….Slide82

So the membrane has capacitance & resistance, as does the

axoplasm

..and we can represent membrane like this…Slide83

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.Slide84

In living mammals, the usual way of activating a neuron…

….is not with stimulators causing threshold or sub-threshold polarizations.

It is with :Slide85

Synaptic TransmissionSlide86

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.Slide87

Postsynaptic EPSP and IPSP:Slide88

Types of synapses:Slide89

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 40A

o

apart.

Ephapses

that make spikes are mostly in invertebrates.

But there are

sub-threshold

ephaptic

influences in mammals.Slide90

Better diagram of A-D, A-SSlide91

Axosomatic micrographsSlide92

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.)Slide93
Slide94

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 0

2

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.)Slide95

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.)Slide96

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.Slide97

This was most persuasively shown..

…by the great Australian neurophysiologist, Sir John Eccles of Canberra (later Buffalo).Slide98

Eccles’ classic demonstrations of Spatial Summation:Slide99

Temporal SummationSlide100

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….Slide101

Eccles did another brilliant demonstration:Slide102

There was more: The second hump= spike could be further “dissected”:Slide103

The inflection points (when 2

nd

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.Slide104

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.Slide105

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.Slide106

The “dynamic duo from

Deutchland

”:

Westecker

&

DeekeSlide107

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.Slide108

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.Slide109

Why is this important? Is there a parallel in nature?

What were those

axo-axonic

synapses all about?Slide110

But in nature, we have no voltage clamps, but we do have

axoaxonic

synapses:Slide111

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.Slide112

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?Slide113

Pre-synaptic Excitation:Slide114

Synaptic Transmission is Chemical. Evidence:

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.Slide115

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).Slide116

Direct Evidence: Loewi’s ExperimentSlide117

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

.Slide118
Slide119

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

. Slide120
Slide121

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 re-absorbed by

presynaptic

cell, so never gets there (across cleft) for degradation…Slide122
Slide123

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

----

 ACHSlide124
Slide125

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.Slide126

1. Cholinergics: Ach.Slide127

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.Slide128
Slide129
Slide130
Slide131

Carlson’s cholinergic

pathways (The point of this slide is to show there are many ACH paths in brain.)Slide132

2. Catecholamines

: a)Epinephrine (adrenalin), b)

Norepinephrine

(

noradrenaline

), c)Dopamine. Mixtures of

a+b

used to be called “

Sympathin

.”Slide133
Slide134
Slide135

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.”)Slide136

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 forebrainSlide137
Slide138

Carlson’s version (Doesn’t show the true origin of VANB!!)Slide139

Dopamine: 1. Afferent collaterals to reticular formationSlide140

Dopamine 2. Nigro-Striate PathSlide141

Indolamines a) Serotonin or 5-hydroxy 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…Slide142

The Raphe-Spinal System of analgesiaSlide143
Slide144

By the way, both catecholamines and

indolamines

are

MonaminesSlide145

Inhibitory amino acid Transmitters:

GABA (Pretty exclusively inhibitory.)

GLYCINE ( +/-)

GLUTAMATE (+/-)

Everywhere in mammals. Slide146

For example, remember this?Slide147
Slide148

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.Slide149

OK, so what are some drugs whose effects are mediated at synapses or axons? (A Mini-course in Psychopharmacology)

Check web site.Slide150

Brief Neuroanatomy. (Good idea to study each day’s lecture each day)Slide151

NOTE:

I will have the opportunity to sneak in an introduction to the topic of neural coding here and there.Slide152

It’s a bit more elaborate.. One needs to fill in details of “CNS”Slide153
Slide154

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:Slide155

BrainStem inside-out organization…Slide156

Cortical projection systemsSlide157

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…Slide158

Cortical Reticular Arousal : stimulate r.f. or any sensory pathSlide159

This change from synchronous (rhythmic) high amplitude, low frequency to

arhythmic

, low amplitude, high frequency is alpha blocking (or arousal of EEG)Slide160

Slightly more realistic….Slide161

Other stuff & illustrative perspective:Slide162

But something is missing from nice up-down/in-out scheme: Cerebellum, important extrapyramidal

structure.Slide163

Side View of Brainstem with CerebellumSlide164
Slide165

Brain Stem Auxilliary(

NO

= not to memorize)Slide166

Visual System NOSlide167

Another view (NO)Slide168

My waySlide169

Different viewSlide170

Auditory pathways NOSlide171

Acoustic receptor cartoon (no)Slide172
Slide173

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 neckSlide174

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).Slide175

Dorsal (posterior)Column SenseNOSlide176
Slide177

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.)Slide178
Slide179
Slide180
Slide181

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) codingSlide182

The predominant view: submodality segregation as in spinal cord

Pain caudally (s.

caudalis

) and non-pain

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).Slide183

But it should have been obvious that saggital knife cuts in TT would likely cut the

nucleus,rostrallySlide184

There was also a “within-line code” suggested by Khayyatt experiment.Slide185

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.Slide186

How to measure facial pain in a rat? Face rub latency, inversely.Slide187
Slide188
Slide189
Slide190

Knife cut experiment:Slide191

How to measure non-pain stimulation of face? Remember this?Slide192

Tested sites on the face:Slide193

Facial Pain Results:Slide194

Non-painful facial stimulation results:Slide195

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!”)Slide196
Slide197

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.Slide198

2. Better Evidence:Slide199

Coolest Evidence:Slide200

CortexSlide201

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.

”