Hippocampal orexin receptors: Localization and function

Orexin (hypocretin) is secreted from the perifornical/lateral hypothalamus and is well known for sleep regulation. Orexin has two, orexin A and B, transcripts and two receptors, type 1 and 2 (OX1R and OX2R), located in the plasma membrane of neurons in different brain areas, including the hippocampus involved in learning, memory, seizures, and epilepsy, as physiologic and pathologic phenomena. OX1R is expressed in the dentate gyrus and CA1 and the OX2R in the CA3 areas. Orexin enhances learning and memory as well as reward, stress, seizures, and epilepsy, partly through OX1Rs, while either aggravating or alleviating those phenomena via OX2Rs. OX1Rs activation induces long-term changes of synaptic responses in the hippocampus, an age and concentration-dependent manner. Briefly, we will review the localization and functions of hippocampal orexin receptors, their role in learning, memory, stress, reward, seizures, epilepsy, and hippocampal synaptic plasticity.