“Apneas” in Purkinje cell activity: evidence for the bistability of membrane potential in the awake cat cerebellum

Abstract

Sustained neural activity can be the result of either the dynamics of recurrent neural networks or the intrinsic properties of individual cells. In the later case, it has been shown in different brain areas that neurons can present a bistable behavior where brief inputs produce a prolonged increase in discharge rate due to a depolarized membrane potential. Neurons in this active condition, the “up-state”, can switch to a hyperpolarized/down-state where they do not fire (O'Donnell and Grace, 1995). In vitro studies in different species have shown that Purkinje cells (PCs) of the cerebellum posses the intrinsic machinery to be considered bistable (Williams et al., 2002). The bistability of membrane potential is manifested in two firing profiles, namely, tonic firing of simple spikes (SSs) in the up-state and pausing periods in the down-state (Loewenstein et al., 2005; Schonewille et al., 2006). These neurons can toggle between both states spontaneously or after brief but significant stimulation in in vitro as well as in anesthetized in vivo preparations using intra and extracellular recordings. However, a recent discrepancy has emerged regarding whether or not PCs in awake animals can toggle from a preponderant up-state to the hyperpolarized condition (Schonewille et al., 2006). Yartsev et al. (2009) confronted these issues using extracellular recordings in the awake, behaving cat. They demonstrated that half of the PCs show long pauses in SSs activity that switched back and forth with periods of continuous firing. These cells, called pausing PCs (PPs), were clearly distinguished from continuous firing PCs using the following quantitative methods: (i) the coefficient of variation in the inter-spike interval (ISI); (ii) the dip test for unimodal instantaneous firing rate; and (iii) a bi-exponential fit to the ISI histogram – only in PPCs two distinct exponentials could be obtained (see Figures 1A (IV), B (IV)). The “apneas” in PCs activity seem to be independent of inhibitory inputs, and they show a duration that is similar to the periods of hyperpolarization observed in intracellular recordings. Hence, bistability inferred indirectly by extracellular recordings may be present in a large portion of PCs in the awake cat.