State-dependent modification of complex spike waveforms in the cerebellar cortex

Abstract

The cerebellum has been the focus of extensive research for more than a century. However, its functional role is still under debate. The comprehensive description of its anatomy and physiology seem to deepen rather than resolve the controversy about its function. Recently, it was shown that Purkinje cells' (PC) membrane potential is bistable and can be found in one of two states: periods of simple spike bursting ("up state"), followed by periods of electrical quiescence and hyperpolarized membrane potential ("down state"). This bistability, which challenges the current dogma regarding the functional organization of the cerebellum, has immediate implications on the mode by which the cerebellar cortex reads incoming input. The well-documented, all-or-none response of PCs to climbing fiber input is generated by complex interactions between the synaptic currents and intrinsic properties of PCs. Hence, it is bound to change as a function of PC membrane potential. Therefore, we compared complex spike waveforms occurring during down and up states, as recorded in both slice preparations and the intact brain of anesthetized rats. We then used the voltage derivative of the intracellular recording to compare the in-vitro intracellular recording to the in-vivo extracellular unit recordings. We found highly significant differences between CSs that occur during the up state and those occurring during the down state. CSs at the up state have a longer duration, and their wavelets have a slower rate of rise than those occurring in the down state. Corresponding changes in the extracellular unit recordings suggests that these changes are manifested in the intact brain. Hence, these state-dependent modifications have immediate, as well as long-term, effects on the output and dynamics of the cerebellar cortex.