Classical Conditioning

Associative

Learning

Nonassociative

Habituation Sensitization

A single type of stimulus The relationship between two stimuli

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 of CS,US: Simultaneous,

delayed (partial overlap in time) or trace (separated in time). Usually strongest conditioning effects for ISI of 200ms-2s.

Circuitry for eyelid conditioning / nictitating membrane response

Single unit recording of complex spike responses of cerebellar Purkinje cells over the course of the behavioral training.

The inferior olive’s ability to convey US to the cerebellum becomes functionally suppressed, as eyeblink conditioning occurs.

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

Cerebellar LTD and Learning-Dependent Timing of Conditioned Eyelid Responses

S.K.E.Koekkoek,H.C.Hulscher,B.R.Dortland,R.A.Hensbroek,Y.Elgersma,T.J.H.Ruigrok,C.I.De Zeeuw*

Science 2003

Inhibition of climbing fibers is a signal for the extinction of conditioned eyelid responses

Medina, Nores and MaukNature 2002

Inhibitory Cerebello-olivary projections and blocking effect in classical conditioning.

Kim, Krupa and ThompsonScience 1998

CR-induced inhibition of the inferiorolive activity is GABA-mediated

US only

CS-US

With PTX

• 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

• 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

Infusion of picrotoxin into the inferior olive prevented extinction of conditioned responses

• Training: five daily sessions

• Extinction protocol with: no infusion ACSF

PTX

Infusion of NBQX into the inferior olive caused extinction of conditioned

responses• Retraining: five daily

sessions• Tone plus unconditioned

stimulus test sessions with: ACSF NBQX (AMPA receptor

antagonist)

• Trial or time dependent influence?

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

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

UR- unconditioned response

Wild-typeWild-type::

Conditioned responses (%)- 80

Average peak amplitude- 0.68

Average peak velocity- 32.6 mm/s

LTD-deficient LTD-deficient micemice::

Conditioned responses (%)- 30

Average peak amplitude- 0.44

Average peak velocity- 19.6 mm/s

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

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’indeed, the mutants’ peak amplitude and peak amplitude and peak velocity weren’t peak velocity weren’t changedchanged..In contrast, those wt In contrast, those wt values were changedvalues 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 Conditioned responses still occur after lesions of the cerebellum in both mutants lesions of the cerebellum in both mutants and wt, but the amplitudes were and wt, but the amplitudes were significantly reducedsignificantly reduced..