Mervyn J. Hardiman

Classical conditioning of the nictitating membrane response of the rabbit

SummaryThe nictitating membrane response (NMR) of 15 rabbits was conditioned to light and white noise conditional stimuli (CSs) using a periorbital shock unconditional stimulus (US). Unilateral lesions of the inferior olive were then made. Lesions restricted to the medial parts of rostral dorsal accessory olive (DAO) and principal olive (PO) abolished conditioning and prevented subsequent acquisition on either side. Unconditional responses to the US were intact. Lesions in all other parts of the olive did not impair conditioning. The effective lesions were located in that part of the olive which supplies somatosensory information from the face to cerebellar lobule HVI. Lobule HVI is also essential for NMR conditioning. We suggest that this region of the inferior olive is part of a circuit which provides US information to the cerebellar cortex during NMR conditioning.

Cerebellar cortex and eyeblink conditioning : a reexamination

SummaryWe examined the effects of cerebellar cortical lesions upon conditioned nictitating membrane responses in rabbits. Using extended postoperative conditioning and unpaired presentations of the conditioned stimuli (CSs), we confirmed that combined lesions of lobules HVI and ansiform lobe abolished conditioned responses (CRs) established to light and white noise CSs. Extended retraining enabled some slight recovery of CR frequencies. Less extensive cortical lesions produced initial abolition of CRs but allowed more complete recoveries. Although CR frequencies and amplitudes were profoundly depressed by cortical lesions, unconditioned response (UR) amplitudes to periorbital electrical stimulation were enhanced. The dissociation of lesion effects upon conditioned and unconditioned responses is consistent with the suggestion that cerebellar cortical mechanisms are important for the learning and execution of eyeblink conditioning.

Reversible inactivations of the cerebellum with muscimol prevent the acquisition and extinction of conditioned nictitating membrane responses in the rabbit

Lesions of the cerebellum severely impair the classically conditioned nictitating membrane response (NMR) in rabbits. Thus, the cerebellum is essential for the production of conditioned responses (CRs), either because it is actively involved in NMR conditioning or because damage to it causes motor or other general deficits. To distinguish between these alternatives, the cerebellum may be inactivated during training. Inactivation of the cerebellum during acquisition training might result in the absence of CRs on initial trials of subsequent training without the neuronal blockade. The blockade may have prevented learning but it may have produced other deficits that require time or further training to overcome. This problem can be addressed by inactivating the cerebellum during extinction training. If inactivation during extinction training results in the immediate production of CRs when training is resumed without the blockade, then it may be concluded that extinction learning was prevented by the blockade — the presence of CRs argues against any deficits not associated with learning. We used muscimol to inactivate the cerebellum and test its involvement in acquisition and extinction of NMR conditioning in the same subjects. We injected muscimol close to the interpositus nucleus of the cerebellum 1 h before each of four daily training sessions of delay conditioning. Almost no CRs were produced in these training sessions — there was little or no acquisition of NMR conditioning during cerebellar inactivation. The subjects were then trained for four daily sessions without injections of muscimol. There were no CRs on initial trials of the first session of retraining, but all subjects produced CRs by the end of this session. The subjects then received four daily sessions of extinction training with muscimol inactivation of the nuclei — no CRs were produced. Extinction training then continued for four daily sessions without muscimol inactivation. On the first of these sessions, all subjects immediately produced high levels of CRs. These responses then extinguished within and between sessions with characteristic beginning-of-session spontaneous recovery. There was little or no extinction of NMR conditioning during cerebellar inactivation. After inactivation, the muscimolinactivated subjects went on to acquire and extinguish NM responses at rates similar to those of appropriate controls. We conclude that cerebellar circuitry is essential for, and actively engaged in, both acquisition and extinction of this simple form of motor learning.

Hippocampal lesions and trace conditioning in the rabbit

Trace conditioning of the nictitating membrane response (NMR) was examined in rabbits with lesions of the dorsal hippocampus and fimbria-fornix. Using a white noise conditional stimulus and an electrical shock unconditional stimulus, the number and amplitude of conditional responses (CRs) was similar in hippocampus-lesioned and control subjects. At some stages of conditioning, the latencies of CRs from hippocampus-lesioned subjects were slightly shorter than those of the controls. We suggest that the hippocampus is not essential for trace conditioning but may exert a modulatory influence on the timing of the CR.

Trace conditioning of the nictitating membrane response in decorticate rabbits

Rabbits with substantial neocortical lesions were given trace conditioning of the nictitating membrane response over a range of interstimulus intervals (ISIs). Unlike hippocampal lesioned animals, which show deficits in such conditioning, the decorticates were not impaired and they gave greater numbers of conditioned responses at longer ISIs than did sham-operated controls. These results suggest that a neocortical-entorhinal input to the hippocampus may not be crucial for trace conditioning.

RETENTION OF CONDITIONED INHIBITION OF THE NICTITATING-MEMBRANE RESPONSE IN DECORTICATE RABBITS

Rabbits were trained on a Pavlovian conditioned inhibition (CI) task using light as the reinforced conditional stimulus (CS) and the same light compounded with a tone as the non-reinforced CS. The conditional response was the nictitating membrane response (NMR). The subjects then received an extensive neocortical lesion or a sham operation. After 9 weeks postoperative recovery, the animals were retrained on the CI task. Sham operated control animals showed immediate and high levels of CI retention but the decorticates showed a profound initial loss, showing that there is a cortical influence in CI. Reacquisition of CI by the decorticates was rapid and showed considerable savings over de novo acquisition. This supports our earlier finding that the neocortex is not essential for the acquisition of CI.