FIGURE 2.

Cellular development of cerebellum and components of the re-entrant cortico-cerebellar loop. (A) Schematic cross sectional view through the anlage of the cerebellum showing the relationship between rhombic lip (rl), ventricular zone (vz), and roof plate (rp) of the fourth ventricle. Adult morphological layering (Figure1) is the product of two major migration pathways. The vz gives rise to GABA-ergic radially dispersed Purkinje cells (oc). The rl generates glutamatergic deep cerebellar nucleus (dcn) neurons and granule cell precursors of the external germinal layer (egl), which migrate tangentially from the rl in sub-pial streams. (B) Postnatally, the egl proliferates under the influence of Purkinje cell-derived Shh. Postmitotic glutamatergic granule cells migrate radially from the EGL to internal granule layer (igl). In mutants where Purkinje cells are deleted, or in which Shh is depleted, or where egl formation is suppressed (as in the Atoh1 knockout mouse), cerebellum growth is reduced. Disruptions in signals from the overlying mesenchyme, directly or through affecting signaling from the roof plate, may modulate the responsiveness of the egl to mitogens, thus abrogating its expansion. (C) From data derived in the primate (Strick et al., 2009) a general model for a mammalian circuit would propose that cortico-cerebellar closed loops modulate cortical activity for a number of different motor and non-motor cortical areas. Without presupposing details of cortical areas in the mouse, cortical activity would be anticipated to feed into the cerebellar circuit via the pontine nucleus, a derivative of the rhombic lip of the hindbrain. Cerebellar output via dentate nucleus neurons would then feed back to the cortical areas via the thalamus.