Learning and memory- Task 4- Classical conditioning and our dearest cerebellum 💕

Unconditioned response

Natural response

Unconditioned stimulus

Natural stimulus that lead to a unconditioned response

Conditioned stimulus

Neutral stimulus that is constantly associated with US

Where is the pathway when pairing loud tone with the former reflexive action?

Now it's not only regulated in lower cognitive areas, it's also regulated by the cerebellum

If ‎ᵦ= 0.2 ==>

On each trial, the weight will change by 20 % EXPL: Trial 1 (no learning): ΔVlight = ‎ᵦ X prediction error 0.2 X 100 = 20 ----> Next time, the animal will have an expectation of the US of 20%

The Resc.- Wagner model to explain: Blocking

Once the animal learned the association V light= 100 --> Prediction error= 100-100=0 If prediction error is 0 --> ΔVlight= ‎ᵦ X prediction error= 0 YOU CAN T LEARN ANYMORE: there is no relevance for the tone to be added

Spontaneous recovery

Tendency for a previously learned association to reappear after a perfiod of extinction (it never disappeared inside)

Prediction error zero means that climbing fibers

can no longer lead to depression of synapses between parallel fibers and PC

3 assumptions of the mathematical model of Rescorla-Wagner

1) A cue has a weight that predicts the US 2)In compound cues, the weight is spread over cues µ 3) Learning corresponds to an increase in cue weight (accumulated over trials), and a corresponding reduction in prediction error. Without prediction error, no learning.

2 equations

1) Prediction Error = Occurrence of US - Expectation of US 2) Increase in cue weight = Learning Rate (‎ᵦ) X Prediction Error

Rescorla- Wagner Model & Error- Correction learning

Amount of change that occurs in the association of a CS and a US depends on a prediction error

The pathway: pons ---> Purkinje cells:

carries a copy of motor commands, visual info...

Climbing fibers

innervate just a few PCs --> Very precise

The aripuff experiment and the conditioning effect, is simple the.... phenomenon

long term depression: just the opposite of long term potentiation: Ca triggers a decrease of neural connectivity (Purkinje cells)

Granule cells, with their parallel fibers make contact with

with hundreds of PCs (= Purkinje cells)

Maybe the inferior olive is where...

you learn when you make mistakes to correct them

Association weight

How strongly the CS predicts the US = How strongly do I know that if I hear a tone, food will come

Cerebellum: structural division

* Anterior lobe * Posterior lobe * Tonsil * Arbor vitae * 2 hemispheres around the vernis * Vernis= Spinocerebellum (in the middle) * Flocculus

Where do mossy fibers and climbing fibers interact?

* At the same Purkinje cells's dendrites (see above) * At the interpositus !!!!

Alternatives to the Resc. and Wagner model:

* Attentional approach to stimulus selection: CS modulation

Can people live without a cerebellum?

* Chinese woman who lived without a cerebellum (diziness, late to learn to speak...) * Young boy who can't speak/walk ---> Yes you can live without it but big imparement

Granular cell layer contains...

*Granule cells *Unipolar brush cells *Golgi cells *Mossy fibers *Climbing fibers

Requirement for an association to be made

*Usefulness *Nonredundant

Mossy and climbing fibers: Respective roles: Mossy fibers (left side)

*carry a plan *bring sensory information

Olivary nucleus receives input from

- the red nucleus (extrapyramidal motor system for involuntary movements, or modulation of voluntary movements) - Corticospinal tract (pyramidal motor system for voluntary movement) - Somatotopic proprioceptive and skin receptors

Mossy and climbing fibers: Respective roles: Climing fibers (right side)

...carry info on execution and error (feedback)

Cerebellar syndroms= Cerebellar ataxia

4 types of incoordination 1) Walking: lesion of the spinocerebellum 2) Limb movements:lesions of the hemispheres of cerebellum (if right hemisphere -> right part of the body SURPRISING) 3)... JUST TO GIVE ME AN IDEA ????

In inferior Olive: Reduction of response

= reduction of prediction error. When the prediction error decreases (the association becomes more and more certain) --> Inf. ol. nuclei inhibit the airpuff signals --> the climbing fibers are useless

Latent inhibition

A familiar stimulus takes longer to acquire meaning than a new one When a group has already been prexposed to the tone (CS), they learn way slowlier than a control group. ----> The model doesn't explain this phenomena because it should be that both prediction error are the same since no association was taught in either cases-> Learning rate shoudl be the same CONDITIONING CAN NOT BE ONLY EXPLAINED BY THE RESCURLA WAGNER MODEL

Extinction

A previously acquired association diminishes throught repeated presentation of the CS in the absence of the US (If the truck tone is heard several times but there is no ice-cream truck coming)

Kamin's blocking effect

Association is impaired if, during the conditioning process, the CS is presented together with a second CS that has already been associated with the unconditioned stimulus

Eyeblink experiment

Aversive conditioning US: Airpuff UR: Blink CS: Tone CR: Blink --> The rabbit blinks at the tone because predicts airpuff is coming

Example conditioned stimulus

Bell

Super important structure for classical conditioning

CEREBELLUM

Non redundant

CR can't be competing with another cue for the same US because its usefulness is blocked by the co-occuring cue

Usefulness

CS provides valuable new info that helps the animal predict the future

Cerebellum for language:

Cerebellum's role is to correct motor movement, with feedback from sensory info ---> Learning to talk really needs this

Δcue weight =

Change in cue weight

Where does the feedback that will lead to the inhibition of the olivary comes from?

Climbing fibers have the sensory info --> Inhibition of the Purkinje Cells -> Inhibition at interpositus -> Inhibition at the olive LOOOP

The Resc.- Wagner model to explain: Why removing one of two compound cues leads to weaker CR

Compound conditioning: Expected US is the sum of the weights of all the cues presented in that trial. So let's say you are trying to associate light and tone, with some food. TRIAL 1: It's the same ΔV light = ‎ᵦ X prediction error= 0.20 X 100= 20 ΔV tone = ‎ᵦ X prediction error= 0.20 X 100= 20 --> Expected US= 20 + 20 = 40 --> Prediction error= 100- 40= 60 TRIAL 2: It's different... ΔVlight = ‎ᵦ X prediction error= 0.20 X 60= 12 ΔV tone = ‎ᵦ X prediction error= 0.20 X 60= 12 ---> ΔVlight = ‎ΔV tone= 20 + 12 = 32 If it would have been only light: ΔVlight = 36 (don't ask me why) BUT THAT DOES NOT MEAN THAT YOU LEARN FASTER IN WITH A SINGLE CUE: The individual weight rise more slowly in compound conditioning but since the overal expected US is calculated as the sum of them --> it raises way more quickly Even is V light = V tone = 50 ---> Prediction error= 100 - (50+50)= 0 It's completly learned

Prediction error

Difference between whether the animal expects the US and whether the US actually occurs

Ionotropic

Excite the activation of PCs on glutamate

Exposure approach to alcohol abuse

Exposure to the particular triggers that set off the problematic behavior. HOW? * We unlearn the association by presenting the cue without alcohol following (BUT IT IS HARD FOR HUMANS BECAUSE COMPLEX HISTORY OF ABUSE) *We reinforce alternative beh (cue -> drink water)

Posterior part of the cerebellum=

Flocculus: vestibular functions

Example unconditioned stimulus

Food

When you present the tone and then the airpuff; inside the PCs

From Pontine nucleus (CS), -> Mossy fibers -> glutamate you have increased activity in PCs and some ionotropic are tagged but not internalized Then from Olivary nucleus (US): parallel fibers activate these sleeping ionotropic receptors -> they don't work anymore -> only the metabotropic receptors are left, which results in decrease of activity in PCs (long term depression for PCs)

Output pathway

From Purkinje cells --> Interpositus nuclei (in deep nuclei) -> Red nuclei

Canonical circuit of the cerebellum=

General make up of the circuit that is abundant throughout the cerebellum

Prediction error=Occurence of US - Expectation of US

High prediction error if the US followed and you failed to predict it

Example of the assumption 2

If in trial 1: only light -> Vlight = Expectation of US If in trial 2: light and tone -> Vlight + Vtone = Expectation of US

Where is the cerebellum located in the cranium?

In the posterior cranial fossa

2nd time PCs receive input: US (airpuff) input pathway to the cerebellum

Inferior olivary nucleus (medulla obligada of brainstem) {VIA climbing fibers }: * -> Cerebellar cortex { VIA fibers connecting with Purkinje cells' dendrites} --> Aspartate: open Aspartate channels are open--> Calcium gets in -> increase in PKC and -> Glu ionotropic receptor that were tagged are removed from the membrane * -> Interpositus nucleus (in deep nuclei region) -> Red nucleus (above in brainstem) -> Down the spinal cord for motor info

Metabotropic

Inhibit the activation of PCs on glutamate Activate an enzyme cascade that internalize ionotropic receptors-> for the metabotropic receptors to be left alone and have complete inhibitory effect

Mossy fibers and climbing fibers

Interact at the site of Purkinje cells to... * modify or adapt ongoing movements (NOT MUSCLES) * on a more permanent basis particular movements (= learning)

LIMITATION OF THE MODEL

Latent inhibition ---> Need for alternatives: The Resc. & Wagner model is based on the US modulation

The different layers in cerebellum

Molecular layer Purkinje cells layer Granular cells layer White matter layer

Lateral part of the cerebellum hemisphere=

Motor planing, higher cog. functions

CS modulation theories

The way the potential CS is processed determines which of the CSs will be associated with the US TO EXPLAIN LATENT INHIBITION

How does the cerebellum contributes to motor learning?

Plasticity of the synapse between parallel fibers and Purkinje cells: When Purkinje cells are activated by the climbing fibers, all the parallel fibers that were recently active go under long-term depression --> Next time the specific parallel fiber is active, it will have a lesser excitatory effect on Purkinje cells (Because the AMPA receptors have been re-absorbed and so --> less power)

1st time PCs receive input: CS (light/tone) input pathway to the cerebellum

Pontine nuclei (in pons of brainstem) {VIA mossy fibers -> granules cells -> parallel fibers} to the Purkinje cells --> At parallel fibers: Glutamate is released -> Activation of ionotropic (AMPA) (+)and metabotropic receptors (-). + Metabotropic activated --> Protein kinases in cell is activated -> Enzyme cascade that tag (=phospholorize) the AMPA receptors that were just activated

The airpuff experiment at first: when no conditioning yet

Puff air --> Blink: Reflex Not regulated by higher cognitive areas (NOT IN THE CEREBELLUM)

Purkinje layer contains...

Purkinje cells

Interoreceptive

Receptors inside the body

Increase in cue weight =

Reduction of prediction error

Conditioned response

Response of the conditioned stimulus, anticipatory

Example conditioned response

Salivation

Example unconditioned response

Salivation

Extroreceptive

Skin receptors, outside the body

Molecular layer contains...

Stellate and basket cells

Blocking in humans: Experiment

Students have to categorize figures in class A, B,C... They make the association that all circles are class A... THEN another cue appears: a little dot that also indicates which class the figure belongs to by its position THEN they don't have the same shapes, only the little dot ))> They can't categorize the figures anymore because they never paid attention to this second cue

Error-correction rule

The Rescorla- Wagner Model and error- Correction learning says that we learn trial-by-trial, by making mistakes, to adjust/ correct the association between CS and US (= to reduce the prediction erro)

THE BIG DIFFERENCE BETWEEN CR AND UR

The action is the same but the CR arrives before the US because it's an anticipatory action

Δcue weight = Learning rate (‎ᵦ) X prediction error

The change in cue weight (ΔVcue) is equal to a constant (‎ᵦ) multiplied by the prediction error

Withdrawal syndrom

The cues are present -> Compensatory responses (CRs) but the drug is not coming -> Imballance in homeostasis -> Craving to reach the balance again

Where are the Purkinje cells located?

Top surface layers of the cerebellum: Dendritic tree spreading in the outside part Soma in Purkinje cell layer Axon that projects to the inside of the cerebellum

Karmin's experiment

Trains rats that a light predicts a shock and then a light + a tone predict a shock --> Rats don't associate well with the tone alone to predict the shock because it didn't improve the ability to predict--> BLOCKING: the first association (light -> shock) was enough

IF ΔV cue < 0 -->

V cue decreases (you don't learn anything)

iF ΔV cue >0 -->‎

V cue increases (you learn a positive association)

Central part of the cerebellum=

Vernis: for motor control of the limbs...

Mackintosh

We have limited capacity to process incoming info --> You can only pay attention to one stimulus. ---> If the "choosed" stimulus was not followed by any US repeatedly, you just ignore this stimulus--> You don't give a chance to any other stimulus

Appetitive conditioning

When US is pleasant

Aversive conditioning

When US is unpleasant

What happens between mossy fibers and climbing fibers?

When conditioning worked: At the olivary nucleus, you have an inhibition that matches the input ---> they cancel each other out --> no signals coming up from climbing fibers BUT IF THEY ARE NOT IDENTICAL --> Signals from climbing fibers -> Update of the plans -> Descending signal from Purkinje cells down to the spinal cord to update the movement LOOOOP

Arbor vitae

White matter/Axons that spread around to the different parts of the cerebellum

If weight of light (Vlight) = 100 --->

You believe that light will predict an airpuff in 100% of cases ---> You will close your eye --> No error, always close your eye

If ‎ᵦ is a big value (still between 0 and 1) -->

You learn fast --> There is a big gap between V cue between 2 trials => ΔV cue is big‎

If ‎ᵦ is a small value (always between 0 and 1) -->

You learn slowly

The higher the prediction error -->

You seem to not learn the association (but you have more opportunity to learn though)

Internalization of receptors=

You take them out of the postsynaptic membrane (they are eaten up)

Conditioned compensatory response

Your body knows that you are in a situation where you will probably receive adrenaline (which will increase your heartbeat)--> To keep homeostatis; anticipatory decrease in heartbeat --> THATS WHY YOU WILL NEED LARGER DOSIS NEXT TIME

A CS light would travel via......... than a CS tone

another subregion of the pontine nuclei

the interpositus always wants to...

fire;; always want to eyeblink!

Purkinje cells characteristics

flat --> so that the dendritic tree of neightboring PCs are in parallel planes

The salivation arrives before the actual...

food is seen

Interpositus wants to fire all the time (so would lead to blinking all the time), but is

inhibited by high activity in Purkinje cell (PC)

Unlearning an association (CS doesn't predict US anymore) takes

more time than learning an association in the beginning

Somatotopic maps in the...

pontine nuclei, inferior olive and in spinocerebellum (you can see like a homunculus in the spinocerebellum (=center): FOR THE INPUT Depending on where the input comes from (=which part of the spinal cord), different subregions of the olivary nucleus (but always stays inside the olivary nucleus) BUT FOR THE OUTPUT Depending on where the output needs to go (which part of the body), you will use different part of the deep cerebellar nuclei

The conditioned response...... the....

preceeds the unconditioned stimulus

If there is calcium inside the cell

protein kinases --> change inside the cell

Microzones in different regions of cerebellar cortex

that are associated with the same body site, are grouped together in a single multizonal microcomplex

Granule cells extend up to the Purkinje cells layer, to form...

the parallel fibers (axons split and can enervate many Purkinje cells)

The climbing fibers need to be activated around...

the same time that the mossy fibers were activated. Like that, the tagged AMPA receptors will be removed --> More metabotropic receptors -> For the same amount of glutamate: hyperpolarization of the PC s

The Rescorla-Wagner model illustrates that classical conditioning is a...

way of reducing error

‎ᵦ

‎Learning rate; constant between 0 and 1

Types of cells in cerebellum

• Purkinje cells • Granular cells • Interneurons - Golgi cells - Basket cells - Stellate cells

Cerebellum is ideally situated to exert motor control

• Receives sensori-motor input from association cortex, spinal cord, vestibular apparatus • Monitors from that input the appropriateness of posture, smooth goal directed movements, and contributes to error-correction • Motor learning in development • Skill learning in adults