Vestibular ganglion neurons survive the loss of their cerebellar targets

Abstract

Neuronal survival during mammalian development crucially depends on target-derived neurotrophic factors. Target loss removes this trophic support and leads in most cases to the transsynaptic retrograde degeneration of the respective afferents. Primary vestibular afferents (PVA) originating from bipolar neurons in the vestibular ganglion (VG) are the first mossy fibers that enter the cerebellum, but little is known about the survival requirements of VG neurons. In the present study the influence of the differential granule cell (GC) target loss on the survival of VG neurons was studied quantitatively using unbiased stereological methods in the cerebellar mutants Purkinje cell degeneration (pcd/pcd), Lurcher (Lc/+), and Weaver (wv/wv). Neither the secondary GC loss in the Purkinje cell deficient mutants pcd/pcd and Lc/+, nor the primary loss of GCs in wv/wv produced any significant reduction in the total number of bipolar neurons in the VG compared to controls. So, PVA neurons are highly resistant to cerebellar target deprivation and survive in the absence of cerebellar granule and Purkinje cells, regardless of whether the target loss occurs before (in wv/wv), during (in Lc/+) or after (in pcd/pcd) the mossy fiber-granule cell synaptogenesis.