by Germund Hesslow
Associative learning in the cerebellum underlies motor memories and probably also cognitive associations. Pavlovian eyeblink conditioning is a widely used experimental model of such learning. Here, a neutral conditional stimulus (CS) such as a tone is repeatedly paired with a reflex-eliciting unconditional stimulus (US) such as an air puff to the cornea. After training, the tone itself elicits a conditioned blink response (CR). The learning is known to depend on the cerebellum, but the locus within the cerebellum as well as the underlying mechanisms has remained controversial. Most investigators follow proposals by Marr and Albus that the CS is transmitted by mossy and parallel fibres to the Purkinje cells in the cerebellar cortex whereas the US is transmitted by climbing fibres which cause synaptic changes in the cerebellar cortex. I will present recordings from single Purkinje cells showing that paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibers) consistently causes a gradual acquisition of an inhibitory response in Purkinje cell simple spike firing. This conditioned cell response matches many known features of the behavioral conditioned response such as its timing. I also summarise some findings concerning a feedback loop from the cerebellum to the inferior olive, where the US is relayed. Finally, I will discuss how this negative feedback loop can control learning and explain some classical puzzles in learning theory such as the observation that simultaneous presentations of two CSs to which the animal has learned to respond individually, cause extinction.