Nitric oxide facilitates GABAergic neurotransmission in the cat oculomotor system: a physiological mechanism in eye movement control.

Abstract

Nitric oxide (NO) synthesis by prepositus hypoglossi (PH) neurons is necessary for the normal performance of horizontal eye movements. We have previously shown that unilateral injections of NO synthase (NOS) inhibitors into the PH nucleus of alert cats produce velocity imbalance without alteration of the eye position control, both during spontaneous eye movements and the vestibulo-ocular reflex (VOR). This NO effect is exerted on the dorsal PH neuropil, whose fibres increase their cGMP content when stimulated by NO. In an attempt to determine whether NO acts by modulation of a specific neurotransmission system, we have now compared the oculomotor effects of NOS inhibition with those produced by local blockade of glutamatergic, GABAergic or glycinergic receptors in the PH nucleus of alert cats. Both glutamatergic antagonists used, 2-amino-5-phosphonovaleric acid (APV) and 2,3-dihydro-6-nitro-7-sulphamoyl-benzo quinoxaline (NBQX), induced a nystagmus contralateral to that observed upon NOS inhibition, and caused exponential eye position drift. In contrast, bicuculline and strychnine induced eye velocity alterations similar to those produced by NOS inhibitors, suggesting that NO oculomotor effects were due to facilitation of some inhibitory input to the PH nucleus. To investigate the anatomical location of the putative NO target neurons, the retrograde tracer Fast Blue was injected in one PH nucleus, and the brainstem sections containing Fast Blue-positive neurons were stained with double immunohistochemistry for NO-sensitive cGMP and glutamic acid decarboxylase. GABAergic neurons projecting to the PH nucleus and containing NO-sensitive cGMP were found almost exclusively in the ipsilateral medial vestibular nucleus and marginal zone. The results suggest that the nitrergic PH neurons control their own firing rate by a NO-mediated facilitation of GABAergic afferents from the ipsilateral medial vestibular nucleus. This self-control mechanism could play an important role in the maintenance of the vestibular balance necessary to generate a stable and adequate eye position signal.