Differential Effects of the Lateral Hypothalamus Lesion as an Origin of Orexin and Blockade of Orexin-1 Receptor in the Orbitofrontal Cortex and Anterior Cingulate Cortex on Their Neuronal Activity.

Introduction: Introduction: Several studies have demonstrated that orexins may regulate different forms of affective and cognitive processes during wakefulness. The Orbitofrontal Cortex (OFC) and Anterior Cingulate Cortex (ACC), as an essential part of the Prefrontal Cortex (PFC), have a crucial role in cognitive processes such as reward and decision-making. They also have a high amount of orexin receptor type 1 (OX1Rs). Methods: In the present study, we inhibited OX1Rs in this area after a 10-min baseline recording to find out the role of OX1Rs in the OFC neuron's firing rate. Next, we inhibited the lateral hypothalamus (LH) as the primary source of orexinergic neurons. Afterward, using a single-unit recording technique in rats, we detected the effects of the lateral hypothalamus on the firing rate and activity pattern of the ACC or OFC neurons. Results: Data showed that the blockade of OX1Rs in the OFC could excite 8 and inhibit 1 neuron(s) out of 11. In addition, the blockade of OX1Rs in the ACC could excite 6 and inhibit 3 neurons out of 10. LH inactivation excited 5 out of 12 neurons and inhibited 6 in the ACC. It also excited 8 and inhibited 6 neurons out of 14 in the OFC. These data suggest that the blockade of OX1Rs excites 72% of the neurons, but LH inactivation had a stimulating effect on only 50% of neurons in two main subregions of the PFC. Conclusion: Accordingly, PFC neurons may receive the orexinergic inputs from the LH and indirectly from other sources. Highlights: Blockade of orexin receptors 1 in ACC alter neural activity in this region.Blockade of orexin receptors 1 in OFC alter neural activity in this region.Lateral hypothalamus inhibition increase neural activity of only 50% neurons in ACC and OFC. Plain Language Summary: The discovery of the neuropeptide orexin/hypocretin in 1998 and subsequent research during the past 20 years revealed an important role for the lateral hypothalamus (LH) in driving the reward pathway, sleep and awake circuits, decision making and psychotic disorders. But our knowledge towards the function of this neurotransmitter on neural activity in specific areas of the brain is limited. In this study we decided to clear the specific role of orexin receptors placed in the two crucial areas of medial prefrontal cortex (mPFC) and the orexin projections from LH on neural firing rates in those regions. In the present study, we investigated the following items by using an in vivo extracellular single-unit recording technique in rats and our data shown that the effect of blocking of orexin receptors1 in mPFC caused a different results than inhibition of the origin of orexin projection in LH as a source of it.