Climbing fiber regulation of spontaneous Purkinje cell activity and cerebellum dependent blink responses

Abstract

It has been known for a long time that GABAergic Purkinje cells in the cerebellar cortex, as well as their target neurons in the cerebellar nuclei, are spontaneously active. The cerebellar output will, therefore, depend on how input is integrated into this spontaneous activity. It has been shown that input from climbing fibers originating in the inferior olive controls the spontaneous activity in Purkinje cells. While blocking climbing fiber input to the Purkinje cells causes a dramatic increase in the firing rate, increased climbing fiber activity results in reduced Purkinje cell activity. However, the exact calibration of this regulation has not been examined systematically. Here we examine the relation between climbing fiber stimulation frequency and Purkinje cell activity in unanesthetized decerebrated ferrets. The results revealed a gradual suppression of Purkinje cell activity, starting at climbing fiber stimulation frequencies as low as 0.5 Hz. At 4 Hz, Purkinje cells were completely silenced. This effect lasted an average of two minutes after the stimulation rate was reduced to a lower level. We also examined the effect of sustained climbing fiber stimulation on overt behavior. Specifically, we analyzed conditioned blink responses, which are known to be dependent on the cerebellum, while stimulating the climbing fibers at different frequencies. In accordance with the neurophysiological data, the conditioned blink responses were suppressed at stimulation frequencies of 4 Hz or higher.

Significance Statement The cerebellum is vital for many important functions including predicting sensory events, adjusting reflexes, allowing smooth movements and acquiring associations between different stimuli. Purkinje cells, in the cerebellar cortex, have a spontaneous activity that is regulated by climbing fiber input from the inferior olive. Here we show that stimulating climbing fibers result in a frequency dependent suppression of Purkinje cell activity. Moreover, such stimulation abolishes the expression of conditioned blink responses, which are known to rely on the cerebellum. These results demonstrate that cerebellar function is crucially dependent on normal levels of spontaneous activity in Purkinje cells.