Abstract
Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depend on activation of TRPC3, and that this property is relevant for all cerebellar functions.DOI: http://dx.doi.org/10.7554/eLife.02536.001.
Highlights
Resolving structure–function relations remains one of the main challenges of modern neuroscience
Purkinje cells were identified by the presence of simple spike (SS) and complex spikes (CSs) and the consistent presence of a pause in SS firing after a CS (Figure 1C–F)
As a biomarker, can be associated with the modular organization of the olivo-cortico-nuclear circuit (Brochu et al, 1990; Voogd et al, 2003; Pijpers et al, 2006; Sugihara and Shinoda, 2007), our results indicate that Purkinje cells within the same module operate around a preferred range of intrinsically determined SS firing frequencies and that this activity is different from modules with a different zebrin identity
Summary
Resolving structure–function relations remains one of the main challenges of modern neuroscience. The unique cyto-architecture of the cerebellum is characterized by the crystalline matrix of its sagittally oriented PC dendrites and climbing fibers and its orthogonally running parallel fibers (Larsell, 1972; Voogd, 2011). The ubiquitous nature of this relatively simple matrix throughout all lobules and modules of the cerebellar cortex made scientists predict in 1967 that this neuronal machine was probably the first to be elucidated (Eccles, 1967). About half a century later, we have collected a wealth of information about the molecular and physiological identity of the various cell types in the cerebellum (Gao et al, 2012), but gross structure–function relations are still largely lacking. Even most slice physiology studies do not discriminate between lobules or modules, indicative of the fact that the cerebellum is still considered physiologically homogeneous
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