Orexin enhances firing activities of neurons in neonatal rat sublaterodorsal tegmental nucleus

Abstract

Objective To investigate the effect and underlying mechanism of orexin in modulating the firing activties of sublaterodorsal tegmental nucleus (SLD) neurons and its possible role in mediating rapid eye movement (REM) sleep regulation. Methods Immunostaining for vglut1, GAD 67, orexin-1/2 receptors and NeuN was performed on brain slices of male adult rats to characterize the distribution pattern of orexin signaling machineries in the SLD. Whole-cell patch-clamp recordings were conducted to investigate the modulatory effect of orexin on membrane potential level and sub-threshold membrane potential oscillations of SLD neurons in brain slices from neonatal SD rats(8~14 d old), and the contribution of these orexin-elicited modulations to the firing activities of SLD neurons was analyzed. Results Immunostaining results showed that the vast majority of SLD neurons were positive for vglut1 and orexin-1/2 receptors. In current-clamp configurations, orexin elicited obvious depolarization in the membrane potential (P < 0.01) and increased the delta (1~4 Hz, P < 0.05) and theta (4~12 Hz, P < 0.05) band power in sub-threshold membrane potential oscillations of SLD neurons. The locking phase of SLD neuronal spikes was pre-shifted in sub-threshold delta oscillations(P < 0.05), and the stability of sub-threshold theta oscillation increased significantly in the presence of orexin(P < 0.05), resulting in enhanced firing activities of SLD neurons. Conclusion Orexin enhances the firing activities of SLD neurons by eliciting the depolarization of the membrane potential and modulating the sub-threshold membrane oscillations of the neurons, and thus plays a role in REM sleep regulation.

Keywords

• orexin
• sublaterodorsal tegmental nucleus
• neuronal activity
• sub-threshold oscillations