[Possible mechanisms for orexin effects on the functioning of the hippocampus and spatial learning (analytical...

We analyzed possible mechanisms for the influence of the "wakening hormone" orexin on spatial learning acting via changes in the functioning of the hippocampus and connected structures. The literature data point out that, firstly, orexin can directly potentiate excitation of neurons in different hippocampal areas by acting on Gq/11-protein-coupled postsynaptic OX1 and OX2 receptors. Due to facilitation of induction of the long-term potentiation of excitatory transmission at each stage of trisynaptic pathway through the hippocampus, orexin can promote transduction of information through this structure and formation of neural representations of object-place associations. Secondly, orexin can increase the release of acetylcholine, GABA and glutamate in the hippocampus by enhancing activity of neurons in the medial septum that have OX1 and OX2 receptors. This could lead to changes in intensity and frequency of the hippocampal theta rhythm. Thirdly, orexin can influence the functioning of reinforcing networks that include neurons of the hippocampus, prefrontal cortex, amygdala, ventral striatum, and ventral tegmental area by direct modulation of their activity through OX receptors. By enhancing the activity of dopaminergic neurons and increasing dopamine release, orexin can improve the functioning of reinforcing networks and facilitate spatial learning.