Cerebellum, delay and trace eyeblink conditioning

UnrestrictedThe cerebellum has a very well organized anatomy. It is recognized for its critical role in the control of movements. For many years, eyeblink conditioning procedures have been used extensively in rabbits and currently in rats and mice to study the role of the cerebellum in motor learning and memory. The paired presentation of the neutral conditioned stimulus (CS) with the noxious unconditioned stimulus (US) produces the learned behavioral conditioned response (CR) – appropriately timed eyeblink. The CS consists typically of a tone or a flashing light whereas the US consists typically of an airpuff into the eye. The mapping of the circuitry essential for eyeblink conditioning has been shown to be successful especially in the standard delay paradigm. The convergent inputs of parallel and climbing fibers at the Purkinje cells, and mossy and climbing fiber collaterals at the deep cerebellar interpositus nuclei provide two simultaneous coincidence detection pathways for conditioned stimulus (CS) and unconditioned stimulus (US). Different types of synaptic plasticity are exhibited in these two pathways in the cerebellar cortex and deep cerebellar nuclei, establishing the cerebellum as a motor learning machine. The memory storage sites of the eyeblink conditioning paradigms have been investigated, and the overwhelming evidence supports the view that the memory is stored in the interpositus (IP) nucleus. The cerebellar cortical circuit helps in acquiring the normal CR in terms of the acquisition rate and the appropriate timing. Trace conditioning – another variant of the eyeblink conditioning paradigm and a simple model of declarative memory – has been shown by many authors to require many more brain areas during memory processes – acquisition, retention, and retrieval – but little is known about the responsible circuitry.; The experiments conducted here emphasize the differential role of the cerebellar cortex and the IP nucleus in standard delay eyeblink conditioning and enhance our understanding of the memory storage site in trace eyeblink conditioning. We hypothesized that the IP nucleus is important as a site of memory storage in both delay and trace eyeblink conditioning. The following experiments employed eyeblink conditioning training while muscimol was infused into either the cerebellar cortex or the IP nucleus at the time before or after the training depending on training procedures of each experiment. In the delay conditioning experiment, the data indicated that the post-training inactivation of both the cerebellar cortex and the IP nucleus did not prevent the acquisition of the memory, and the pre-training inactivation of only the IP nucleus, but not the cerebellar cortex, inhibited the expression of the previously learned memory. In the trace conditioning experiment, the data showed that the pre-training inactivation of the IP nucleus, before the learning of trace eyeblink conditioning, prevented the acquisition of the memory and the inactivation after the learning reversibly abolished the expression of the memory. The obtained data support our hypothesis about the importance of the IP nucleus as a memory storage site in both delay and trace eyeblink conditioning