Abstract
Cerebellar cortex has an elaborate rostrocaudal organization comprised of numerous microzones. Purkinje cells (PCs) in the same microzone show synchronous activity of complex spikes (CSs) evoked by excitatory inputs from climbing fibers (CFs) that arise from neurons in the inferior olive (IO). The synchronous CS activity is considered to depend on electrical coupling among IO neurons and anatomical organization of the olivo-cerebellar projection. To determine how the CF–PC wiring contributes to the formation of microzone, we examined the synchronous CS activities between neighboring PCs in the glutamate receptor δ2 knockout (GluD2 KO) mouse in which exuberant surplus CFs make ectopic innervations onto distal dendrites of PCs. We performed in vivo two-photon calcium imaging for PC populations to detect CF inputs. Neighboring PCs in GluD2 KO mice showed higher synchrony of calcium transients than those in wild-type (control) mice. Moreover, the synchrony in GluD2 KO mice hardly declined with mediolateral separation between PCs up to ~200 μm, which was in marked contrast to the falloff of the synchrony in control mice. The enhanced synchrony was only partially affected by the blockade of gap junctional coupling. On the other hand, transverse CF collaterals in GluD2 KO mice extended beyond the border of microzone and formed locally clustered ectopic synapses onto dendrites of neighboring PCs. Furthermore, PCs in GluD2 KO mice exhibited clustered firing (Cf), the characteristic CF response that was not found in PCs of wild-type mice. Importantly, Cf was often associated with localized calcium transients in distal dendrites of PCs, which are likely to contribute to the enhanced synchrony of calcium signals in GluD2 KO mice. Thus, our results indicate that CF signals in GluD2 KO mice propagate across multiple microzones, and that proper formation of longitudinal olivo-cerebellar projection is essential for the spatiotemporal organization of CS activity in the cerebellum.
Highlights
The cerebellum consists of several parasagittal zonal compartments elongated along rostrocaudal direction
These results indicate that the synchrony of spontaneous complex spikes (CSs) among neighboring Purkinje cells (PCs) is greatly enhanced in GluD2 KO mice, and the spatial range of synchrony is extended in mediolateral direction
The enhancement of synchrony in mediolateral direction was ascribed to the local calcium transients evoked by clustered firing (Cf) that frequently occurred in close succession to the global calcium transients evoked by CSs
Summary
The cerebellum consists of several parasagittal zonal compartments elongated along rostrocaudal direction (designated A, B, C1–3, and D1–2) These compartments are based on the topography of the olivo-cerebellar projection system that constitutes one of the two major afferent systems to the cerebellum (Groenewegen et al, 1979; Voogd and Glickstein, 1998; Sugihara et al, 2001; Sugihara, 2005). Experiments with a small injection of anterograde tracer into the IO have demonstrated that a small number of adjacent IO neurons project CFs within narrow longitudinal bands of about 200 μm width (Sugihara et al, 2001; Sugihara and Shinoda, 2004), which correspond to physiologically identified microzones (Lang et al, 1999). Because of this anatomical organization and electrical coupling among adjacent IO neurons, CF inputs are synchronized among PCs within a microzone, and the synchrony rapidly falls off as the mediolateral separation between PCs increases (Llinas and Yarom, 1981; Sotelo et al, 1986; Blenkinsop and Lang, 2006; Ozden et al, 2009; Schultz et al, 2009)
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