SUMMARY1. We have examined the role of the anterior interpositus nucleus (AIP) of the cerebellum in Pavlovian conditioning of the nictitating membrane response (NMR) of the rabbit with the use of reversible brain lesions produced by the local anaesthetic lidocaine. Previous experiments have demonstrated that destructive lesions of the AIP prevent the performance of conditioned NMRs (CRs). Microinjections of lidocaine into the AIP were used in the present experiment to determine whether the deficit in the performance of CRs resulted from a deficit in learning or memory.2. A 3-phase procedure was employed to determine whether associative learning required the function of the AIP. In phase 1, rabbits were trained to make CRs to a flashing-light conditioned stimulus (CS) that was paired with an air-puff unconditioned stimulus (UCS) directed at the cornea. In phase 2, the AIP was anaesthetized during a session of conditioning in which a tone CS was paired with the UCS. Presentations of the light CS were interpolated throughout the tone conditioning in order to monitor the degree to which CRs were impaired by lidocaine. Phase 3 occurred after the effects of the lidocaine had dissipated and consisted of a test of retention to determine whether learning occurred during phase 2 but could not be expressed because of a performance deficit resulting from the inactivation of the AIP.3. Infusion of lidocaine into the AIP abolished CRs to the light CS and prevented the performance of CRs to the tone CS in phase 2. The effect of the infusion was specifically due to a conduction block of neurons and/or fibres in the lateral aspect of the AIP. The infusion of lidocaine into regions surrounding the AIP did not affect CRs elicited by the light CS or prevent acquisition of CRs to the tone. Infusions of saline directly into the AIP did not impair the performance of CRs to either the tone or light CS. Quantitative analysis of diffusion revealed that the abolition of CRs was accompanied by anaesthetization of the AIP.4. The retention test in phase 3 indicated that learning occurred normally during phase 2 when the AIP was inactivated and performance was abolished. When the function of the AIP was restored and performance had recovered, the subjects demonstrated a frequency of CRs to the tone CS that was indistinguishable from control subjects whose performance had never been impaired. MS 8897 J. P. WELSH AND J. A. HARVEY 5. The CRs observed during the retention test provided an unequivocal measure of associative learning. Control subjects that received explicitly unpaired presentations of the tone and air puff during the infusion of lidocaine responded at baseline levels to the tone when the function of the AIP was restored.6. We conclude that the AIP is not essential for Pavlovian conditioning of the NMR because learning occurs normally when the AIP is inactivated. Therefore, the AIP can neither be a site where memories for Pavlovian conditioning are stored nor a site that is essential for sensory processing which leads to associat...

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from typically-developing (TD) subjects with regard to learning rate or the timing of the CR. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals.

Classical conditioning of the rabbit nictitating membrane response was accomplished by presenting a 100-msec tone conditioned stimulus at intervals of 0, 100, 200, 400, and 800 msec before the presentation of a 100-msec shock unconditioned stimulus. In addition, tone-alone and shock-alone trials were interspersed during conditioning. On the first day of conditioning, during which there was no evidence of acquisition of conditioned responses to the tone conditioned stimulus, the amplitudes of the nictitating membrane response evoked on paired tone-shock trials were compared with the amplitudes obtained on shock-alone trials to provide a measure of reflex facilitation. There was a significant correlation (+0.86) in control animals between the degree of reflex facilitation and the degree of learning demonstrated at the various tone-shock intervals. Both reflex facilitation and learning were absent at the 0-msec tone-shock interval, increased at the 100-msec interval, reached a maximum at the 200-msec interval, and then declined at the longer intervals. Scopolamine (0.4 mg/kg) did not affect the amplitude of the nictitating membrane response elicited on shock-alone trials but eliminated any evidence of reflex facilitation or learning at the 100- and 800-msec intervals and significantly reduced both reflex facilitation and learning at the 200- and 400-msec intervals. The comparable effects of scopolamine on both reflex facilitation and learning were reflected by a significant correlation (+0.95) between these two measures.(ABSTRACT TRUNCATED AT 250 WORDS)

This study reexamined the effects of unilateral damage to cerebellar hemispheral lobule VI on the rabbit's conditioned nictitating membrane (NM) response. Extensive unilateral removal of hemispheral lobule VI in 11 rabbits impaired ipsilateral conditioned responses as reflected by reductions of 52% in mean frequency and 53% in mean amplitude during test trials on the first postoperative session. The decreases in the amplitude and frequency of conditioned responses were highly correlated (r = 0.82). The frequency of conditioned responses recovered to control levels but their amplitudes remained reduced such that the correlation between these two measures of responding was no longer significant by the 12th postoperative conditioning session. The decrease in the amplitude of conditioned responses was not accompanied by changes in onset latency or rise time. There was no significant impairment of conditioned responses in surgical controls and animals with only partial damage to hemispheral lobule VI. It was concluded that hemispheral lobule VI plays an important role in the regulation of motor centers in the brainstem so as to facilitate the initiation and optimum execution of the conditioned NM reflex. This cortical regulation of the conditioned NM response may contain learned elements; however, these cannot be resolved with lesion methods, nor has their existence been proven in this or other lesion studies. Nevertheless, the results of this study do demonstrate that the cerebellar cortex cannot be considered as the single locus necessary for NM conditioning.

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