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Possible Mechanisms for the Effects of Orexin on Hippocampal Functioning and Spatial Learning (analytical review)

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We present here an analysis of the possible mechanisms for the effects of the “waking hormone” orexin on spatial learning, mediated by changes in the functioning of the hippocampus and structures connected to it. Published data indicate firstly that orexin can directly increase neuron excitation in different hippocampal fields, acting on Gq/11-protein-coupled postsynaptic OX1 and OX2 receptors. By facilitating the induction of long-term potentiation of excitatory transmission in each component of the trisynaptic pathway via the hippocampus, orexin can promote transmission of information through this structure and form neuronal reflections of “object-place” associations. Secondly, orexin can increase the release of acetylcholine, GABA, and glutamate in the hippocampus by potentiating excitation of neurons in the medial septum, which bear OX1 and OX2 receptors. This can result in changes in the extent and frequency of the hippocampal theta rhythm. Thirdly, orexin can affect the functional reinforcement circuit, which includes neurons in the hippocampus, prefrontal cortex, amygdala, ventral striatum, and ventral tegmental area, directly modulating their activity via OX receptors. Acting via increases in the activity of dopaminergic cells and increases in dopamine release, orexin can alter the nature of the functioning of the basal ganglia, improve the functioning of reinforcement circuits, and facilitate spatial learning.

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  1. Institute of Higher Nervous Activity and NeurophysiologyRussian Academy of Sciences, Moscow, Russia

    I. G. Sil’kis

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Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 62, No. 4, pp. 389–400, July–August, 2012.

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Sil’kis, I.G. Possible Mechanisms for the Effects of Orexin on Hippocampal Functioning and Spatial Learning (analytical review). Neurosci Behav Physi 43, 1049–1057 (2013). https://doi.org/10.1007/s11055-013-9849-2

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