Inactivation of the superior cerebellar peduncle blocks expression but not acquisition of the rabbit's classically conditioned eye-blink response.

Abstract

The localization of sites of memory formation within the mammalian brain has proven to be a formidable task even for simple forms of learning and memory.Recent studies have demonstrated that reversibly inactivating a localized region of cerebellum, including the dorsal anterior interpositus nucleus, completely prevents acquisition of the conditioned eye-blink response with no effect upon subsequent learning without inactivation. This result indicates that the memory trace for this type of learning is located either (i) within this inactivated region of cerebellum or (ii) within some structure(s) efferent from the cerebellum to which output from the interpositus nucleus ultimately projects. To distinguish between these possibilities, two groups of rabbits were conditioned (by using two conditioning stimuli) while the output fibers of the interpositus (the superior cerebellar peduncle) were reversibly blocked with microinjections of the sodium channel blocker tetrodotoxin. Rabbits performed no conditioned responses during this inactivation training. However, training after inactivation revealed that the rabbits (trained with either conditioned stimulus) had fully learned the response during the previous inactivation training. Cerebellar output, therefore, does not appear to be essential for acquisition of the learned response. This result, coupled with the fact that inactivation of the appropriate region of cerebellum completely prevents learning, provides compelling evidence supporting the hypothesis that the essential memory trace for the classically conditioned eye-blink response is localized within the cerebellum.Identification of the site or sites of memory formation and storage within the brain for any particular type of memory is an essential prerequisite for elucidating the cellular or subcellular mechanisms as well as the network level properties that mediate the acquisition, retrieval, and expression of that particular memory. Although much progress toward identifying potential sites of memory formation and storage has been achieved, definitive localization of a particular memory locus within the mammalian brain has remained frustratingly elusive. A major obstacle impeding this localization of memory traces is the necessity of first identifying the neural-anatomical circuitry essential for acquisition and expression of a particular learned response. For at least one form of learned behavioraversive, classically conditioned discrete skeletal movements, specifically, the classically conditioned eye-blink responsethe neural circuitry essential for acquisition and expression of the learned response has largely been identified (for review, see ref. 1). In brief, the results of lesion, recording, and stimulation studies indicate that the conditioned stimulus (CS) pathway includes sensory relay nuclei, the pontine nuclei, and mossy fiber projections, via the middle cerebellar peduncle, toThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be he...

Acquisition of a new-latency conditioned nictitating membrane response--major, but not complete, dependence on the ipsilateral cerebellum.

“…When cerebellar efferent fibers, rostral to the cerebellar nuclei in the brachium conjunctivum, are inactivated with tetrodotoxin, performance of CRs is prevented but learning can proceed normally (Krupa and Thompson 1995). In the Welsh and Harvey (1991) study, infusion cannula tip locations were in the dorsal aspect of the interpositus/dentate nuclei in five of the six subjects in the critical group, and distribution of the lidocaine was confirmed with autoradiography of [3H]lidocaine infusions.…”

Differential Effects of Cerebellar Inactivation on Eyeblink Conditioned Excitation and Inhibition

“…Muscimol inactivation of the cerebellum also prevents savings, indicating that no learning occurred during inactivation. Inactivation of efferent nuclei or the superior cerebellar peduncle prevents the expression of CRs during training but has no effect on CR production after the inactivation sessions (Krupa et al, 1993;Krupa and Thompson, 1995). The muscimol inactivation studies indicate that the neural plasticity underlying excitatory conditioning is established within the cerebellum and the efferent systems are necessary for motor performance.…”

Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

“…The mechanisms underlying learning-specific plasticity in the cerebellar deep nuclei may involve changes in neuronal excitability or synaptic potentiation (Aizenman & Linden, 2000;Racine, Wilson, Gingell, & Sunderland, 1986). The output of the learning circuitry is the projection from the deep nuclei to the red nucleus, and from there to the relevant motor nuclei (Chapman, Steinmetz, Sears, & Thompson, 1990;Clark & Lavond, 1993;Desmond, Rosenfield, & Moore, 1983;Krupa & Thompson, 1995;Krupa, Thompson, & Thompson, 1993;Krupa, Weng, & Thompson, 1996;McCormick, Guyer, & Thompson, 1982;.…”