Orexin-1 receptor mediates long-term potentiation in the dentate gyrus area of freely moving rats

Orexin neurons, localized in the lateral hypothalamus area, synthesize two neuropeptides called orexin A and orexin B and send their axons to hippocampal formation including dentate gyrus (DG). Orexin A and orexin B act as endogenous ligands for two G-protein coupled receptors called orexin-1 and orexin-2 receptors (OX1R and OX2R). In the dentate gyrus (DG) region, OX1R, which has high affinity for orexin A, is expressed. Conflicting results have been reported regarding the effect of orexinergic system on synaptic plasticity. When given alone, SB-334867-A, a non-peptide OX1R antagonist, is a suitable drug to assess the natural and physiological significance of endogenous orexins. In the present research, we studied the effects of DG-OX1Rs antagonization on long-term potentiation (LTP) using two different high frequency stimulation (HFS) protocols i.e. 200 and 400 Hz in freely moving rats. The results showed that inactivation of DG-OX1Rs impair LTP induction in both HFS protocols which lasts beyond 24 h. This occurs with respect to both the population excitatory post-synaptic potential slope and population spike amplitude. Our findings suggest that endogenous orexins are involved in the expression of LTP, at least through DG-OX1Rs.

Research highlights▶ Inactivation of orexin-1 receptor in the dentate gyrus area impairs the expression of voltage gated calcium channel dependent LTP in freely moving rats. ▶ Inactivation of orexin-1 receptor in the dentate gyrus area impairs the expression of NMDA receptor-dependent LTP in freely moving rats. ▶ DMSO has no effect on the baseline synaptic response in the dentate gyrus region of the freely moving rats. ▶ The orexin-1 receptors in dentate gyrus area have no effect on the baseline synaptic response in the dentate gyrus region of the freely moving rats.