Pavlovian conditioning in the rabbit during inactivation of the interpositus nucleus.

Abstract

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...

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

“…Accumulated evidence has indicated that both Purkinje cells and interpositus nucleus circuits play a critical role in the execution and proper timing of CRs in associative eyeblink motor learning (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The CS and US signals are conveyed to both the Purkinje cell and the interpositus nucleus circuits, and the convergent information of these two signals is capable of inducing neural plasticity at both circuits (2,26,36,37).…”

“…1a). The localization and underlying mechanisms of eyeblink conditioning have been extensively studied by different approaches including gene targeting (6)(7)(8)(9)(10)(11), lesioning (12)(13)(14)(15), mutant analysis (16), and pharmacological inactivation analyses (17)(18)(19)(20)(21)(22)(23). On the basis of these studies, one model proposes an essential role of the cerebellar Purkinje cell circuit in memory traces (24)(25)(26).…”

Estradiol Improves Cerebellar Memory Formation by Activating Estrogen Receptor β

“…If activated ERs are involved in cerebellar memory formation, one expects that at least some forms of motor learning and cellular plasticity are affected concomitantly by E2. Moreover, if E2 action is mainly cortical and the relationship between the cellular and behavioral effects is causal in a direct manner, one expects that the behavioral effects on the learning are rather specific with relatively mild or no effects on motor performance (Welsh and Harvey, 1991;Jiménez-Díaz et al, 2004). Here we tested the impact of E2 on adaptation of the vestibuloocular reflex (VOR) after visuovestibular training (Robinson, 1976;Ito, 1991;De Zeeuw et al, 1998) (Fig.…”

Selective Impairment of the Cerebellar C1 Module Involved in Rat Hind Limb Control Reduces Step-Dependent Modulation of Cutaneous Reflexes

“…However, because modules may consist of thin and noncontinuous cortical zones (Voogd et al, 2003;), it has not been possible to study the function of a complete module without influencing others. Alternative approaches, e.g., interfering with either the output of the modules, i.e., the cerebellar nuclei (Welsh and Harvey, 1991;Koekkoek et al, 2003), or their input [inferior olive (Welsh and Harvey, 1998)], are similarly restricted by the size and location of these nuclei, resulting either in subtotal lesions or in affecting surrounding regions.…”