Research Inhibition of Nitric Oxide Synthesis and Gene Knockout of Neuronal Nitric Oxide Synthase Impaired Adaptation of Mouse Optokinetic Response Eye Movements

Nitric oxide (NO) plays a key role in synaptic transmission efficiency in the central nervous system. To gain an insight on the role of NO in cerebellar functions, we, here, measured the dynamics of the horizontal optokinetic response (HOKR) and vestibulo-ocular reflex (HVOR), and the adaptation of HOKR in mice locally injected with NG-monomethyl-L-arginine (L-NMMA) that inhibits NO synthesis and in mice devoid of neuronal nitric oxide synthase (nNOS). Local application of L-NMMA into the cerebellar flocculi induced no change in the dynamics of the HOKR but markedly depressed the adaptation of the HOKR induced by 1 hr of sustained screen oscillation. A slight difference was seen in the HOKR but not in the HVOR dynamics between nNOS−/− mutant and wild-type mice. One hour of sustained screen oscillation induced adaptation of the HOKR gains in wild-type mice but not in mutants. These observations suggest that NO is essential for the adaptation of the HOKR and that nNOS is the major enzyme for NO synthesis in the process. Nitric oxide (NO) plays a number of important roles as a biological messenger molecule. In the central nervous sys-tem, the importance of NO in neural plasticity has recently been recognized. In the cerebellum, conjunctive stimuli to parallel and climbing fibers evoke long-term depression (LTD) of synaptic transmission of parallel fiber–Purkinje cell synapses (Ito et al. 1982; Ekerot and Kano 1985). The role of NO in induction of cerebellar LTD was first suggested b