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

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 interspike intervals (ISIs) had a different temporal relationship 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.

[1]  Detlef H. Heck,et al.  A technique for stereotaxic recordings of neuronal activity in awake, head-restrained mice , 2009, Journal of Neuroscience Methods.

[2]  W. T. Thach Discharge of cerebellar neurons related to two maintained postures and two prompt movements. II. Purkinje cell output and input. , 1970, Journal of neurophysiology.

[3]  Shigeru Shinomoto,et al.  Estimating Instantaneous Irregularity of Neuronal Firing , 2009, Neural Computation.

[4]  C. Granger Investigating causal relations by econometric models and cross-spectral methods , 1969 .

[5]  Mingzhou Ding,et al.  Analyzing information flow in brain networks with nonparametric Granger causality , 2008, NeuroImage.

[6]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[7]  R. Llinás,et al.  Dynamic organization of motor control within the olivocerebellar system , 1995, Nature.

[8]  Mingzhou Ding,et al.  Estimating Granger causality from fourier and wavelet transforms of time series data. , 2007, Physical review letters.

[9]  J. Geweke,et al.  Measurement of Linear Dependence and Feedback between Multiple Time Series , 1982 .

[10]  D. Heck,et al.  Cerebellar cortical output encodes temporal aspects of rhythmic licking movements and is necessary for normal licking frequency , 2010, The European journal of neuroscience.

[11]  H. Sompolinsky,et al.  Bistability of cerebellar Purkinje cells modulated by sensory stimulation , 2005, Nature Neuroscience.

[12]  Mingzhou Ding,et al.  Analyzing multiple spike trains with nonparametric granger causality , 2009, Journal of Computational Neuroscience.

[13]  S. Koekkoek,et al.  Spatiotemporal firing patterns in the cerebellum , 2011, Nature Reviews Neuroscience.

[14]  Abigail L. Person,et al.  Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei , 2011, Nature.

[15]  Kamran Khodakhah,et al.  The Linear Computational Algorithm of Cerebellar Purkinje Cells , 2006, The Journal of Neuroscience.

[16]  D. Linden,et al.  Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum. , 1999, Journal of neurophysiology.

[17]  Joy T. Walter and,et al.  The advantages of linear information processing for cerebellar computation , 2009, Proceedings of the National Academy of Sciences.

[18]  M. Yartsev,et al.  Pausing Purkinje Cells in the Cerebellum of the Awake Cat , 2008, Front. Syst. Neurosci..

[19]  E. De Schutter,et al.  Patterns and pauses in Purkinje cell simple spike trains: experiments, modeling and theory , 2009, Neuroscience.

[20]  D. Jaeger,et al.  The Control of Rate and Timing of Spikes in the Deep Cerebellar Nuclei by Inhibition , 2000, The Journal of Neuroscience.

[21]  H. Sompolinsky,et al.  Purkinje cells in awake behaving animals operate at the upstate membrane potential , 2006, Nature Neuroscience.

[22]  Fadi Xu,et al.  Purkinje cell degeneration elevates eupneic and hypercapnic ventilation in rats , 2008, The Cerebellum.

[23]  G. M. Shambes,et al.  Fractured somatotopy in granule cell tactile areas of rat cerebellar hemispheres revealed by micromapping. , 1978, Brain, behavior and evolution.

[24]  B. Antkowiak,et al.  Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices. , 1997, Journal of neurophysiology.