Behavior-Related Pauses in Simple-Spike Activity of Mouse Purkinje Cells Are Linked to Spike Rate Modulation

Abstract

Purkinje cells (PCs) in the mammalian cerebellum express high frequency spontaneous activity with average spike rates between 30 and 200 Hz. Cerebellar nuclear (CN) neurons receive converging input from many PCs resulting in a continuous barrage of inhibitory inputs. It has been hypothesized that pauses in PC activity trigger increases in CN spiking activity. A prediction derived from this hypothesis is that pauses in PC simple spike activity represent relevant behavioral or sensory events. Here we asked whether pauses in the simple spike activity of PCs related to either fluid licking or respiration, play a special role in representing information about behavior. Both behaviors are widely represented in cerebellar PC simple spike activity. We recorded PC activity in the vermis and lobus simplex of head fixed mice while monitoring licking and respiratory behavior. Using cross correlation and Granger causality analysis we examined whether short ISIs had a different temporal relation to behavior than long ISIs or pauses. Behavior related simple spike pauses occurred during low-rate simple spike activity in both licking and breathing related PCs. Granger causality analysis revealed causal relationships between simple spike pauses and behavior. However, the same results were obtained from an analysis of surrogate spike trains with gamma ISI distributions constructed to match rate modulations of behavior related Purkinje cells. Our results therefore suggest that the occurrence of pauses in simple spike activity does not represent additional information about behavioral or sensory events that goes beyond the simple spike rate modulations.

Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules

“…The combination of a high level of activity, even at rest (Zhou et al 2014), and the fact that their output is inhibitory make it tempting to assume that PCs communicate through the absence of action potentials, i.e., pauses (see, e.g., De Schutter and Steuber 2009;De Zeeuw et al 2011). The occurrence and relevance of short (50 -500 ms) and long (Ͼ500 ms) SS pauses under physiological conditions have been a topic under debate for nearly a decade (Cao et al 2012;Cheron et al 2014;Libster and Yarom 2013;Loewenstein et al 2005;Oldfield et al 2010;Schonewille et al 2006;Shin et al 2007;Wang et al 2012;Yartsev et al 2009). Understanding where and under what conditions pauses occur is crucial for evaluating their functional importance.…”

“…This assumption, however, does not explain the eminent difference between the various obtained results. Although other factors, such as species differences, may be at play, the effects of tissue disruption and temperature could also explain the discrepancies between earlier reports on PC pausing behavior (Cao et al 2012;Cheron et al 2014;Loewenstein et al 2005;Schonewille et al 2006;Yartsev et al 2009;Zhou et al 2014). Particularly due to the recent developments in two-photon imaging techniques, recording in vivo has become increasingly popular.…”

“…Next, we examined various features of SS activity that are independent of the mean ISI, or firing rate, as much as possible. To do so, we first determined the occurrence of pauses, for which there is currently no generally accepted definition (Cao et al 2012;Schonewille et al 2006;Shin et al 2007;Yartsev et al 2009). Shin and De Schutter (2006) developed formal criteria to identify pauses, based on the climbing fiber pause, to study the correlation between pairs of PCs.…”

“…2A) in relation to pausing. There is, to our knowledge, no generally accepted ISI duration that constitutes a pause (see, e.g., Cao et al 2012;Loewenstein et al 2005;Schonewille et al 2006;Shin and De Schutter 2006;Yartsev et al 2009). Here, we aimed to identify the ISIs that are decidedly longer than normal ISIs to quantify pausing behavior.…”

“…Long pauses were suggested to be functionally relevant, since whisker stimulation-induced complex spikes can toggle transitions from up-to downstates and vice versa (Loewenstein et al 2005). These conclusions were challenged by other studies, which showed that long SS pauses are rare in awake behaving mice (Cao et al 2012;Schonewille et al 2006) and that the probability is significantly increased by anesthesia . However, the cerebellum is not a homogeneous structure; differences in gene expression, anatomical connectivity, and physiological properties have been identified.…”