Serotonergic Suppression of Sustained Synaptic Responses in Rat Oculomotor Neural Integrator Networks

Neural signals necessary for gaze holding are produced in the excitatory networks of oculomotor neural integrators including the prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC). Our previous studies have shown that the activation of the networks can be evaluated by sustained excitatory postsynaptic current (EPSC) responses in vitro, in which a higher EPSC frequency after burst stimulation (100 Hz, 20 trains) than the frequency before the stimulation lasts for >1 s. Both the PHN and the INC receive serotonergic inputs mainly from the dorsal raphe nucleus, and serotonin (5-HT) induces depolarizing responses via 5-HT₂ or 5-HT₃ receptors and hyperpolarizing responses via 5-HT_1A receptors in PHN and INC neurons. However, how 5-HT affects sustained EPSC responses remains unknown. In this study, we investigated the effects of 5-HT on sustained EPSC responses using whole-cell recordings in brainstem slices obtained from rats of either sex. Compared with the control treatment, bath application of 10 μM 5-HT significantly reduced the duration and frequency of the EPSC responses in the PHN and the INC. The application of 8-OH-DPAT, an agonist of the 5-HT_1A receptor, suppressed sustained EPSC responses, but agonists of the 5-HT₂ and 5-HT₃ receptors had no effect on the responses, indicating that 5-HT has a suppressive effect on sustained EPSC responses via 5-HT_1A receptors. These results suggest that neurons that express 5-HT_1A receptors participate in excitatory networks and that the suppressive effect of 5-HT can facilitate exploratory behavior through eye movements rather than gaze holding.