Initial localization of the acoustic conditioned stimulus projection system to the cerebellum essential for classical eyelid conditioning.

Abstract

Previous experiments have demonstrated a sufficient and necessary involvement of mossy fibers in projecting conditioned stimulus information to the cerebellum during classical eyelid conditioning in rabbits. Presented here are electrophysiological, anatomical, and lesion data that suggest that cells within the lateral pontine nuclear region may be essentially involved in projecting information concerning the occurrence of acoustic conditioned stimuli to the cerebellum during classical conditioning.A number of theories concerning cerebellar function have postulated a role for the cerebellum in motor learning (1-5). A common theme is that cerebellar plasticity is thought to be due to the conjunctive activation of mossy and climbing fibers on a common element, the Purkinje cell, whose axons project ventrally to cerebellar and brainstem nuclei. In our laboratory, a number of lesion, recording, and stimulation studies have demonstrated that the cerebellum is critically involved in the acquisition and retention of classically conditioned skeletal muscle responses (6)(7)(8)(9)(10)(11)(12)(13)(14). From these data we have proposed that neuronal plasticity involved in acquisition and retention of conditioned responses (CRs) is localized to regions of the cerebellum where the conditioned stimulus (CS) and the unconditioned stimulus (US) converge, and that the CS is projected to the cerebellum along mossy fibers while the US is projected to the cerebellum along climbing fibers (15).We have demonstrated the essential involvement of climbing fibers in projecting the US to the cerebellum during classical conditioning. First, lesions placed in rostromedial portions of the dorsal accessory olive (DAO) prevent acquisition in naive rabbits and cause behavioral extinction with continued training in rabbits given lesions after acquisition training (16, 17). Second, stimulation of the DAO-cimbing fiber system, which produces a variety of behaviors (e.g., eyeblink, head turn, limb flexion) can serve as an effective US for classical conditioning (18)(19)(20) MATERIALS AND METHODS Acute Electrophysiological Recording. Twelve male albino rabbits were anesthetized with halothane, the skull above the right pontine nuclei was removed, and the entire extent of the right pontine nuclei and an area 2 mm caudal to the nuclei was mapped for auditory evoked field potentials. Mapping consisted of systematically lowering an insulated, stainless steel recording electrode (50-gm exposed tip) in 1 mm increments to obtain recordings from the entire right pontine nuclei, ventral portions of the right ventral nucleus of the lateral lemniscus (NVLL), and rostral areas of the right superior olive (SO) and trapezoid nucleus (NTB). Three clicks (65 decibels sound pressure level) were presented at each recording site via a speaker located 10 cm from the right ear, and auditory-evoked field potentials were bandpass filtered at 100-1000 Hz, digitized, and stored for further analysis. At the end of the recording session, electrolytic marking lesions wer...

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

“…Thus, the present experiment could rule out the possibility that stimulation of the caudal mPFC significantly activates other areas of cortex. In addition, the lesion and field potential data suggest that the lateral pontine nuclei conveys necessary CS signals to the cerebellum in eyeblink conditioning [79,80] . Recent studies suggest that mossy fiber activity driven by input from mPFC www.chinaphar.com Wu GY et al Acta Pharmacologica Sinica npg to lateral pontine nuclei which persists through the stimulusfree trace interval to overlap in time with the US supports the auditory TEC [6,75,76] .…”

Evaluation of bidirectional interstimulus interval (ISI) shift in auditory delay eye-blink conditioning in healthy humans

“…This lack of an association between CSevoked ERPs and measures of learning is in accordance with animal work on CS processing. It is well established that the lateral pontine nucleus represents the primary projection system for CS input into the cerebellum (Bao, Chen, & Thompson, 2000;Freeman & Rabinak, 2004;Freeman, Rabinak, & Campolattaro, 2005;Gould, Sears, & Steinmetz, 1993;Hesslow, Svensson, & Ivarsson, 1999;Knowlton & Thompson, 1988;Lewis, LoTurco, & Solomon, 1987;Steinmetz, 1990b;Steinmetz, Lavond, & Thompson, 1989;Steinmetz et al, 1987;Steinmetz, Rosen, Chapman, Lavond, & Thompson, 1986;Steinmetz & Sengelaub, 1992;Tracy, Thompson, Krupa, & Thompson, 1998). While there are projections from auditory cortices to the pontine (Knowlton et al, 1993), it appears that an intact auditory cortex is not necessary for conditioning to occur (Knowlton & Thompson, 1992;Oakley & Russell, 1977).…”

Ethanol-exposed neonatal rats are impaired as adults in classical eyeblink conditioning at multiple unconditioned stimulus intensities

“…CS sensory information is relayed to the cerebellum through mossy fibers in the basilar pontine nuclei (Steinmetz et al, 1987;Steinmetz and Sengelaub, 1992), while US sensory information is relayed to the cerebellum via climbing fiber neurons in the inferior olive complex (McCormick et al, 1985;Sears and Steinmetz, 1991). Associative synaptic plasticity is thought to occur in neurons that receive convergent CS-US inputs-in particular, neurons in the interpositus (IP) nucleus and Purkinje cells in the cerebellar cortex.…”