Synaptic Mechanism for the Sustained Activation of Oculomotor Integrator Circuits in the Rat Prepositus Hypoglossi Nucleus: Contribution of Ca2+-Permeable AMPA Receptors

Abstract

Sustained neural activity is involved in several brain functions. Although recurrent/feedback excitatory networks are proposed as a neural mechanism for this sustained activity, the synaptic mechanisms have not been fully clarified. To address this issue, we investigated the excitatory synaptic responses of neurons in the prepositus hypoglossi nucleus (PHN), a brainstem structure involved as an oculomotor neural integrator, using whole-cell voltage-clamp recordings in rat slice preparations. Under a blockade of inhibitory synaptic transmissions, the application of "burst stimulation" (100 Hz, 20 pulses) to a brainstem area projecting to the PHN induced an increase in the frequency of EPSCs in PHN neurons that lasted for several seconds. Sustained EPSC responses were observed even when the burst stimulation was applied in the vicinity of a recorded neuron within the PHN that was isolated from the slices. Pharmacologically, the sustained EPSC responses were reduced by 1-naphthyl acetyl spermine (50 μm), a blocker of Ca(2+)-permeable AMPA (CP-AMPA) receptors. Analysis of the current-voltage (I-V) relationship of the current responses to iontophoretic application of kainate revealed that more than one-half of PHN neurons exhibited an inwardly rectifying I-V relationship. Furthermore, PHN neurons exhibiting inwardly rectifying current responses showed higher Ca(2+) permeability. The sustained EPSC responses were also reduced by flufenamic acid (200 μm), a blocker of Ca(2+)-activated nonselective cation (CAN) channels. These results indicate that the sustained EPSC responses are attributable to the sustained activation of local excitatory networks in the PHN, which arises from the activation of CP-AMPA receptors and CAN channels in PHN neurons.