An Associative Memory Trace in the Cerebellar Cortex

Detta är en avhandling från Department of Experimental Medical Science, Lund Univeristy

Sammanfattning: Classical conditioning of motor responses, e.g., the eyeblink response, depends on the cerebellum. In the theoretical works of David Marr (1969) and James Albus (1971), it was proposed that Purkinje cells in the cerebellar cortex learn to associate the neutral conditioned stimulus with the response. Since their work, several studies have provided data that are consistent with this suggestion, but definitive evidence has been lacking. Information on how Purkinje cells change their activity during learning has been ambiguous and contradictory and there has been no information at all about how they behave during extinction and reacquisition. The electrical activity of single Purkinje cells was recorded with microelectrodes in decerebrate ferrets during learning, extinction, and relearning. We demonstrate that paired peripheral forelimb and periocular stimulation, as well as paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibres) consistently causes a gradual acquisition of an inhibitory response in Purkinje cell simple spike firing. The response also displays gradual extinction to unpaired presentations of the stimuli, and reacquisition with substantial savings when paired stimulus presentation is reinstated. This conditioned Purkinje cell response thus has several properties that match known features of the conditioned eyeblink response across training trials. The temporal properties of the conditioned Purkinje cell response were also investigated. The response maximum was adaptively timed to precede the unconditioned stimulus. The latencies to response onset, maximum, and offset varied with the interstimulus interval used during training. Further training with changes in the interstimulus interval caused new learning of response latencies. Finally, short-term manipulations of the conditioned stimulus after training had effects on the Purkinje cell response that match effects on the conditioned eyeblink response. These data suggest that many of the behavioural phenomena in eyeblink conditioning can be explained at the level of the single Purkinje cell.

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