Different Activation Mechanisms of Excitatory Networks in the Rat Oculomotor Integrators for Vertical and Horizontal Gaze Holding

Gaze holding in the horizontal and vertical directions is separately controlled via the oculomotor neural integrators, the prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC), respectively. Our previous in vitro studies demonstrated that transient, high-frequency local stimulation of the PHN and the INC increased the frequency of spontaneous EPSCs that lasted for several seconds. The sustained EPSC response of PHN neurons was attributed to the activation of local excitatory networks primarily mediated via Ca(2+)-permeable AMPA (CP-AMPA) receptors and Ca(2+)-activated nonselective cation (CAN) channels. However, the contribution of CP-AMPA receptors to the activation of INC excitatory networks appeared to be small. In this study, we clarified the mechanisms of excitatory network activation in the PHN and INC using whole-cell recordings in rat brainstem slices. Although physiological and histological analyses showed that neurons that expressed CP-AMPA receptors existed not only in the PHN but also in the INC, the effect of a CP-AMPA receptor antagonist on the sustained EPSC response was significantly weaker in INC neurons than in PHN neurons. Meanwhile, the effect of an NMDA receptor antagonist on the sustained EPSC response was significantly stronger in INC neurons than in PHN neurons. Furthermore, the current and the charge transfer mediated via NMDA receptors were significantly larger in INC neurons than in PHN neurons. These results strongly suggest that these excitatory networks are activated via different synaptic mechanisms: a CP-AMPA receptor and CAN channel-dependent mechanism and an NMDA receptor-dependent mechanism in horizontal and vertical integrators, respectively.