Neuronal Nitric Oxide synthase regulates the expression of EAAT4 and GAD65/67 in the murine cerebellum

The cerebellum is a brain structure that is responsible for coordinating voluntary movement such as balance, coordination, and posture. Purkinje neurons (PNs) are the sole GABAergic output from the cerebellar cortex and receive major excitatory inputs via parallel fibers (PFs) that produce high levels of nitric oxide (NO) via neuronal nitric oxide synthase (nNOS). Previous studies demonstrate that nNOS/NO signaling is crucial for PF-PN synaptic transmission. This study sought to examine nNOS/NO signaling regulation of excitatory amino acid transporter 4 (EAAT4) on PN dendrites and glutamic acid decarboxylase (GAD) expression/function between sexes by using wildtype (WT) and nNOS-/- mice at different postnatal developmental time points. This study revealed that there are gene- and sex-dependent differences in GABA concentration in the cerebellum during early postnatal development. Additionally, there is decreased EAAT4 expression in male nNOS-/- mice. Lastly, there is decreased GAD65/67 expression in both male and female nNOS-/- nice compared to age-matched WT mice. Our results provide new knowledge of NO regulation of cerebellar synaptic transmission, which may advance the development of cerebellar ataxia therapeutics