Feedback control of cerebellar learning

Abstract: The ability to anticipate future events and to modify erroneous anticipatory actions is crucial for the survival of any organism. Both theoretical and empirical lines of evidence implicate the cerebellum in this ability. It is often suggested that the cerebellum acquires “expectations” or “internal models”. However, except in a metaphorical sense, the cerebellum, which consists of a set of interconnected nerve cells, cannot contain “internal models” or “have expectations”. The aim of this thesis is to untangle these metaphors by translating them back into neurophysiological cause and effect relationships. This task is approached from within the paradigm of classical conditioning, in which a subject, through repeated presentations of a conditional stimulus, followed by an unconditional stimulus, acquires a conditioned response. Importantly, the conditioned response is timed so that it anticipates the unconditioned response. Available neurophysiological evidence suggests that Purkinje cells, in the cerebellar cortex, generate the conditioned response. In addition, Purkinje cells provide negative feedback to the IO, which is a relay for the unconditional stimulus, via the nucleo-olivary pathway. Purkinje cells can therefore regulate the intensity of the signal derived from the unconditional stimulus, which, in turn, decides subsequent plasticity. Hence, as learning progresses, the IO signal will become weaker and weaker due to increasing negative feedback from Purkinje cells. Thus, in an important sense, learning induced changes in Purkinje cell activity constitute an “expectation” or “anticipation” of a future event (the unconditional stimulus), and, consistent with theoretical models, future learning depends on the accuracy of this expectation. Paper 1 in this thesis show that learned changes in Purkinje cells influences subsequent IO activity. The second paper show that, depending on the number of pulses it contains, the signal from the IO to the Purkinje cells can either cause acquisition or extinction. In the third paper we present evidence that can potentially help explain overexpectation, a behavioral phenomenon, which have for long been elusive. Collectively these papers advance our understanding of the feedback mechanisms that govern cerebellar learning and it proposes a potential solution to some long standing behavioral conundrums.