The cerebellum is a brain region that is associated with proprioception (the ability to sense the position of limbs in space), and has a protracted developmental period. Research suggests that postnatal development of the Purkinje cell (PC) layer in the cerebellum of rodents is dependent on neural activity. PC development is characterized by polyinnervation of climbing fiber inputs from the inferior olive during postnatal week one, and by postnatal week two, PCs are predominantly innervated by a single climbing fiber. One contributor to PC development is thought to arise from changes in neural activity due to proprioceptive feedback of myoclonic twitches observed during active (or REM) sleep. To further examine the role of neural activity on cerebellar development in infant rodents, we used postnatal day 8-9 (P8) and postnatal day 14-15 (P15) mice. Mice with a conditional knockout (KO) of the ErbB2 gene in skeletal muscles were compared with wildtype (WT) littermates. The ErbB2 gene is essential for the development of muscle spindles, which are integral to proprioceptive feedback. We hypothesized that KO mice would exhibit less climbing fiber innervation due to diminished proprioceptive feedback during development. To test this, we observed labeling of vesicular glutamate, an excitatory neurotransmitter, of climbing fibers in the somatic and molecular layers of KO mice in comparison with WT controls. Results showed that P15 KO mice have smaller PC diameter and less climbing fiber translocation than WTs. This suggests that proprioceptive feedback from muscle spindles to the cerebellum is an important provider of neural activity during PC development and climbing fiber translocation.
Ashley Brodell, ’16
Sponsor: Sue Astley