Heterogeneity of Purkinje cell simple spike–complex spike interactions: zebrin‐ and non‐zebrin‐related variations

Abstract

Purkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS-associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the amplitudes of the SS modulation phases were generally weak. Division of spikelets into likely axonally propagated and non-propagated groups (based on their interspikelet interval) showed that the correlation of spikelet number with SS firing rate primarily reflected a relationship with non-propagated spikelets. In sum, the results show both zebrin-related and non-zebrin-related physiological heterogeneity in SS-CS interactions among PCs, which suggests that the cerebellar cortex is more functionally diverse than is assumed by standard theories of cerebellar function.

Cerebellar Modules and Their Role as Operational Cerebellar Processing Units

“…By this technique, synchronous complex spike activity in PCs within a module has been clarified [ 49 ]. Some different properties of PCs belonging to different modules have also become evident [ 50 ], as described in other sections of this article. Module-specific climbing and mossy fiber axonal projections have been revealed [ 10 , 51 ].…”

“…However, the use of anesthetics affects the regularity of PC firing [ 135 ], potentially explaining why the opposite result, higher regularity in ZII+ PCs, was found in awake mice [ 133 ]. Common finding in both studies is that some variations in other parameters are not related to zebrin patterning, suggesting further heterogeneity in PCs [ 50 , 133 , 136 ]. Overall, these results confirm a module-related differentiation of PCs, the sole output of the cerebellar cortex.…”

Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules that are defined by distinct pinceau sizes

“…ZebrinII-positive Purkinje cells were reported to have lower frequencies and more regularity, whereas zebrinII-negative Purkinje cells have a higher firing frequency and a more irregular pattern of activity (Zhou et al, 2014; Xiao et al, 2014). Moreover, consistent with the highly organized convergence of mossy fibers and climbing fibers within dedicated zones (Voogd et al, 2003), in vivo electrophysiology recordings demonstrate zone-specific interactions in simple spike and complex spike activity (Tang et al, 2017). Interestingly, during development there is a converse relationship such that Purkinje cell activity itself is required for precisely shaping the zones into fine-grained compartments (White et al, 2014).…”

Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

“…Compared with vehicle-injected PDAPP mice, the transplantation of iPSC-derived differentiated neuronal precursor cells to PDAPP mice significantly improved memory dysfunction [29]. Purkinje cells are the only neurons in the cerebellar cortex that automatically produce two types of action potentials [30]. Damage to Purkinje cells is related to cognitive impairment and motor deficits in patients with AD [31].…”