Emergence of a 600-Hz buzz UP state Purkinje cell firing in alert mice

• We examine the emergence of 600-Hz buzz UP state of Purkinje cell in alert mice.
• Climbing fiber input is able to switch the 600-Hz buzz to the DOWN state.
• 600 Hz increases the CS frequency indicating inferior olive disinhibition.
• A single PC model is able to reproduce the 600-Hz buzz.

Purkinje cell (PC) firing represents the sole output from the cerebellar cortex onto the deep cerebellar and vestibular nuclei. Here, we explored the different modes of PC firing in alert mice by extracellular recording. We confirm the existence of a tonic and/or bursting and quiescent modes corresponding to UP and DOWN state, respectively. We demonstrate the existence of a novel 600-Hz buzz UP state of firing characterized by simple spikes (SS) of very small amplitude. Climbing fiber (CF) input is able to switch the 600-Hz buzz to the DOWN state, as for the classical UP-to-DOWN state transition. Conversely, the CF input can initiate a typical SS pattern terminating into 600-Hz buzz. The 600-Hz buzz was transiently suppressed by whisker pad stimulation demonstrating that it remained responsive to peripheral input. It must not be mistaken for a DOWN state or the sign of PC inhibition. Complex spike (CS) frequency was increased during the 600-Hz buzz, indicating that this PC output actively contributes to the cerebello-olivary loop by triggering a disinhibition of the inferior olive. During the 600-Hz buzz, the first depolarizing component of the CS was reduced and the second depolarizing component was suppressed. Consistent with our experimental observations, using a 559-compartment single-PC model – in which PC UP state (of about −43 mV) was obtained by the combined action of large tonic AMPA conductances and counterbalancing GABAergic inhibition – removal of this inhibition produced the 600-Hz buzz; the simulated buzz frequency decreased following an artificial CS.