Pausing Purkinje cells in the cerebellum of the awake cat

Abstract

A recent controversy has emerged concerning the existence of long pauses, presumably reflecting bistability of membrane potential, in the cerebellar Purkinje cells (PC) of awake animals. It is generally agreed that in the anesthetized animals and in vitro, these cells switch between two stable membrane potential states: a depolarized state (the ‘up-state’) characterized by continuous firing of simple spikes (SS) and a hyperpolarized state (the ‘down-state’) characterized by long pauses in the SS activity. To address the existence of long pauses in the neural activity of cerebellar PCs in the awake and behaving animal we used extracellular recordings in cats and find that approximately half of the recorded PCs exhibit such long pauses in the SS activity and transition between activity – periods with uninterrupted SS lasting an average of 1300 ms – and pauses up to several seconds. We called these cells pausing Purkinje cells (PPC) and they can easily be distinguished from continuous firing Purkinje cells. In most PPCs, state transitions in both directions were often associated (25% of state transitions) with complex spikes (CSs). This is consistent with intracellular findings of CS-driven state transitions. In sum, we present proof for the existence of long pauses in the PC SS activity that probably reflect underlying bistability, provide the first in-depth analysis of these pauses and show for the first time that transitions in and out of these pauses are related to CS firing in the awake and behaving animal.

Dendritic Calcium Signaling Triggered by Spontaneous and Sensory-Evoked Climbing Fiber Input to Cerebellar Purkinje Cells In Vivo

“…In addition, our data showing similar state-dependent changes in [Ca 2ϩ ] transients under light anesthesia appear to be inconsistent with the lower prevalence of bistability in awake mice (Schonewille et al, 2006). Although this issue is still debated (Loewenstein et al, 2005;Schonewille et al, 2006;Tal et al, 2008;Rokni et al, 2009;Yartsev et al, 2009), one possible explanation is that increased background and evoked parallel fiber input in the awake state could override the hyperpolarization that represents the transition from up to down state. In that case, we would expect bistability to be modulated by wakefulness and not by anesthetic level.…”

“…We did not observe [Ca 2ϩ ] changes associated with spontaneous up-down or down-up transitions that were not triggered by CS (data not shown). In addition, given that membrane potential bistability of Purkinje cells in physiological (awake) conditions and the role of CS in state transitions are highly debated (Loewenstein et al, 2005;Schonewille et al, 2006;Yartsev et al, 2009), we questioned whether the correlation between peak amplitude of CF-triggered [Ca 2ϩ ] transients and state transitions of the cell is dependent on the depth of anesthesia. We therefore repeated the experiments under relatively light anesthesia (0.5-1% isoflurane).…”

“…Under our recording conditions, i.e., wholecell recordings under anesthesia, Purkinje cells exhibit bistability in membrane potential ( Fig. 3A) (Loewenstein et al, 2005;Tal et al, 2008;Rokni et al, 2009;Yartsev et al, 2009). To investigate the contribution of membrane potential bistability to the CFtriggered Ca 2ϩ signal, we first classified the observed [Ca 2ϩ ] transients depending on whether the CS occurred in the depolarized "up" state (associated with simple spike firing) or in the quiescent, hyperpolarized "down" state ( Fig.…”

Climbing Fibers Control Purkinje Cell Representations of Behavior

“…Accurate performance on this task requires continuously monitoring the salient behavioral parameters and adjusting for mismatches in hand movement relative to target movement (Hewitt et al, 2011;Popa et al, 2012). This task subverts overly learned, stereotypic behaviors, such as reaching and saccades, in which movement parameters are correlated (Paninski et al, 2004;Soetedjo et al, 2008). It is possible that, during more stereotypic movements, particular aspects of the behavior dominate the CS and SS modulation with little need to adjust the information in the SS firing.…”

Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states

“…In experiments performed in vivo and in slices, complex spikes recorded from Purkinje cells have been correlated to state changes in Purkinje cells (5,7,8,12). It has been shown that single stimuli to the parallel fibers, which originate from within the cerebellar cortex, can cause bursts of action potentials in Purkinje cells, which terminate with a brief pause in Purkinje cell firing, hypothesized to result from an increased Ca 2+ sensitive K + conductance (13,14).…”