Simple and complex spike responses of mouse cerebellar Purkinje neurons to regular trains and omissions of somatosensory stimuli

Abstract

Cerebellar Purkinje neurons help compute absolute subsecond timing, but how their firing is affected during repetitive sensory stimulation with consistent subsecond intervals remains unaddressed. Here, we investigated how simple and complex spikes of Purkinje cells change during regular application of air puffs (3.3 Hz for ~4 min) to the whisker pad of awake, head-fixed female mice. Complex spike responses fell into two categories: those in which firing rates increased (at ~50 ms) and then fell (complex spike elevated "CxSE" cells), and those in which firing rates decreased (at ~70 ms) and then rose (complex spike reduced "CxSR" cells). Both groups had indistinguishable rates of basal complex (~1.7 Hz) and simple (~75 Hz) spikes, and initially responded to puffs with a well-timed sensory response of a short-latency (~15 ms), transient (4 ms) suppression of simple spikes. CxSE more than CxSR cells, however, also showed a longer-latency increase in simple spike rate, previously shown to reflect motor command signals. With repeated puffs, basal simple spike rates dropped greatly in CxSR but not CxSE cells; complex spike rates remained constant, but their temporal precision rose in CxSR cells and fell in CxSE cells. Also over time, transient simple spike suppression gradually disappeared in CxSE cells, suggesting habituation, but remained stable in CxSR cells, suggesting reliable transmission of sensory stimuli. During stimulus omissions, both categories of cells showed complex spike suppression with different latencies. The data indicate two modes by which Purkinje cells transmit regular repetitive stimuli, distinguishable by their climbing fiber signals.

Influence of data sampling methods on the representation of neural spiking activity in vivo

“…Complex spikes are modulated by input from climbing fibers originating in the inferior olive, and occur between 1 and 2 spike/s ( Table 1 ). 30 , 77 , 78 , 79 , 80 Both simple spike and complex spike firing rates fluctuate during recording sessions in mice ( Figure 3 B). We analyzed how sample durations influence firing rate, CV, and CV2 estimates using the three analyses previously described ( Table 1 , n = 17).…”

“…We hypothesized that accurate descriptions of nuclei neuron and Purkinje cell baseline firing activity required longer sample durations because only longer durations captured sufficient firing rate modulating events. 29 , 30 , 56 , 67 , 81 By this logic, firing rate variability was underestimated in shorter sample durations because the range of firing rates that modulate sensorimotor events was perhaps insufficiently sampled. If fewer different events modulate a neuron’s firing pattern, a shorter sample duration would be necessary to accurately describe that neuron’s firing pattern.…”

“… 28 , 29 , 91 , 92 Similarly, the presentation of an abundance of olfactory, visual, auditory, and somatosensory stimuli during recordings in both awake and anesthetized mice results in fluctuations in the firing rate of cerebellar neurons. 30 , 83 , 84 The same stimulus or action must be repeated many times to find the mean change in neural activity to the stimulus or action, or to map a change in the neural activity onto that stimulus or action. In transient recordings, it is unlikely that the same activity or stimulus is repeated sufficient times to relate changes of activity to a specific event.…”

“…Purkinje cells and nuclei neurons have intrinsic properties that allow them to generate remarkably regular action potentials even without input from other neurons. 25 , 26 , 27 However, sensory and motor afferents modify these intrinsic firing properties in the intact cerebellum of live animals, 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 resulting in highly dynamic firing properties in the in vivo circuit.…”

“… 38 However, the presence of the chosen anesthetic and particular anesthesia regime can also affect the firing features of neurons 65 , 66 and anesthesia-induced immobility could limit sensorimotor-related changes in neural firing. 29 , 30 , 56 , 67 , 68 , 69 Likewise, fluctuations in firing properties associated with the relative arousal state of the animal may be relevant to ongoing behavior. 70 , 71 , 72 This raises the question, within the constraints of standard experimental settings, how can we ensure that biologically relevant differences are represented in the spiking activity of single neurons when comparisons are made between experimental groups?…”