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...

Relative cerebral glucose metabolism was examined with positron-emission tomography (PET) as a measure of neuronal activation during performance of the classically conditioned eyeblink response in 12 young adult subjects. Each subject received three sessions: (i) a control session with PET scan in which unpaired presentations of the tone conditioned stimulus and corneal airpuff unconditioned stimulus were administered, (ii) a paired training session to allow associative learning to occur, and (iii) a paired test session with PET scan. Brain regions exhibiting learningrelated activation were identified as those areas that showed significant differences in glucose metabolism between the unpaired control condition and well-trained state in the 9 subjects who met the learning criterion. Areas showing significant activation included bilateral sites in the inferior cerebellar cortex/deep nuclei, anterior cerebellar vermis, contralateral cerebellar cortex and pontine tegmentum, ipsilateral inferior thalamus/red nucleus, ipsilateral hippocampal formation, ipsilateral lateral temporal cortex, and bilateral ventral striatum. Among all subjects, including those who did not meet the learning criterion, metabolic changes in ipsilateral cerebellar nuclei, bilateral cerebellar cortex, anterior vermis, contralateral pontine tegmentum, ipsilateral hippocampal formation, and bilateral striatum correlated with degree of learning. The localization to cerebellum and its associated brainstem circuitry is consistent with neurobiological studies in the rabbit model of eyeblink classical conditioning and neuropsychological studies in braindamaged humans. In addition, these data support a role for the hippocampus in conditioning and suggest that the ventral striatum may also be involved.Eyeblink conditioning is a basic form of associative learning that has been studied extensively in humans since the 1930s. Animal models of this form of conditioning have demonstrated close behavioral parallels with human conditioning, lending support to the hypothesis that the learning shares common neurobiological substrates in humans and other mammals (1). Eyeblink conditioning is well-suited for neurobiological analyses because the use of appropriate unpaired control procedures can help distinguish between areas of the brain that are responding to the sensory stimuli or the motor response and those that are selectively activated under paired learning conditions. This feature makes the paradigm an ideal candidate for neurobiological analysis in humans using positron-emission tomography (PET) to identify regions of the brain that are specifically activated under paired training conditions relative to unpaired control procedures.Although eyeblink conditioning is a seemingly simple form of learning, under normal conditions it appears to involve the interaction of diverse brain systems. Neurobiological studies (conducted primarily in rabbits) have identified the cerebellum and its brainstem connections as essential components of the eyeblink condit...

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