Introduction to Neurobiology Lecture 13: Classical conditioning 1.

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Transcript of Introduction to Neurobiology Lecture 13: Classical conditioning 1.

Introduction to NeurobiologyLecture 13: Classical conditioning 1

Associative

Learning

Nonassociative

Habituation Sensitization

A single type of stimulus

The relationship between two stimuli or reward .

Classical

conditioning Operant

conditioning Extinction

Blocking

Definitions

An Unconditioned stimulus (US) is a stimulus which “naturally” elicits an (unconditioned) response (UR). For example:An airpuff to the eye is an unconditioned stimulus which elicits an eyeblink (nictitating membrane response).

A conditioned stimulus (CS) is a “neutral” stimulus (e.g. a tone), which, by being associated with the US, leads after learning to a conditioned response (CR).

Basic paradigm

Before learning,US URCS nothing

Training:CS+US URCS increasing CR(=UR)

Post-training:CS CR (=UR).Temporal relationship :

1 )Simultaneous 2 )Delayed (partial overlap in time)

3 )Trace (separated in time. Usually 200ms-2s.

The nictitating membrane response

Circuitry for conditioning nictitating membrane response

The suppression of CF during learning of eye blink.

Naive animal

Trained animal

US only

CS-US

With PTX

GABA is involved in the suppression of CF.

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Extinction protocol with :no infusion

ACSF PTX

GABA is involved in the extinction of CR.

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The response of trained animal to tone + puff

test sessions with: ACSF

NBQX (AMPA receptor antagonist)

AMPA receptors are involved in the extinction of CR.

Blocking: CS “A” is tone; CS “B” is light; US is air puff.The eyeblink response to air puff is the UR The Eyeblink response to A or B is the CR

B+US C

RB

A+B+US C

RA/BA+US

A+B+USCR

ACR

B //

CR

AA+US

Blocking of conditioned eyelid responses

Phase I, animals received seven daily sessions of tone-airpuff conditioning ;Phase II, animals underwent five sessions of tone-light-airpuff compound conditioning.Either picrotoxin )PTX) or )ACSF) was infused directly into the inferior olive.Controls experienced only the second phase of the blocking procedure .

Afterward, all animals were presented with light-airpuff pairings to assess whether conditioning to the light had accrued during compound conditioning )phase II).

Both control and PTX animals exhibited significant learning to the light CS compared with the ACSF animals - blocking did not occur in the PTX group.

PTX had no effect on the performance of CRs and URs during the compound conditioning, indicating that PTX selectively affected blocking.

ACSF

PTX

CONTROL

Phase 1 phase 2 phase 3

Blocking

GABA is involved in blocking of conditioned eyelid responses

Circuitry for conditioning nictitating membrane response

Wild-type:

Conditioned responses (%)- 80

Average peak amplitude- 0.68

Average peak velocity- 32.6 mm/s

LTD-deficient mice:

Conditioned responses (%)- 30

Average peak amplitude- 0.44

Average peak velocity- 19.6 mm/s

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Average CS-alone responses of a wild-type animal and a L7-PKCi mutant

At T-4 (but not at T-2) the wt shows well-timed responses around the US onset time.

The response peak of the mutant doesn’t change.

At T-4 (but not at T-2) there are changes between wt and the mutant.

Blue- wild typeRed- mutants

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Average CS-alone responses when the ISI is extended to 500 ms

If the timing is LTD-dependent, the amplitude and velocity in the L7-PKCi mutant should not be influenced by the length of the ISI.

indeed, the mutants’ peak amplitude and peak velocity weren’t changed.

In contrast, those wt values were changed.

Blue- wild typeRed- mutants

Red - pre-lesion

Blue – post-lesion

Green - post-sham lesion

Mutants wt

)After T-4)

Conditioned responses still occur after lesions of the cerebellum in both mutants and wt, but the amplitudes were significantly reduced.

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Blocking neuronal activity in cerebellar output

Superior cerebellar peduncle blocked using perfusion of TTX

Expression of eyeblink conditioning blocked, but not acquisition

Krupa and Thompson, PNAS 1995

The cerebellar-olivary system

LTD

LTP

1.2Hz<>Rate

phase 1 : seven daily sessions of tone-airpuff conditioning.

phase 2 : five sessions of tone-light-airpuff compound conditioning while either PTX or ACSF was infused.

phase 3 : all animals were presented with light-airpuff pairing tests.

controls experienced only the second phase of the blocking procedure.

Blocking of conditioned eyelid responses

olivepons

PF CF

PC’s

LTD

DCN

CR

Blocking: US inhibition

US CS

PTX: blocks inhibition

prevents blocking

prevents extinction

Extinction: without US or with NBQX

The daily training consisted of 10 blocks of 10 trials.

The trials were separated by a random intervals )20 to 40 ms).

Response of wild-type )wt) after 2 days and after 4 days.CR- conditioned response

UR- unconditioned response