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Publication : Spatial memory requires hypocretins to elevate medial entorhinal gamma oscillations.

First Author  Liao Y Year  2024
Journal  Neuron Volume  112
Issue  1 Pages  155-173.e8
PubMed ID  37944520 Mgi Jnum  J:358732
Mgi Id  MGI:7565229 Doi  10.1016/j.neuron.2023.10.012
Citation  Liao Y, et al. (2023) Spatial memory requires hypocretins to elevate medial entorhinal gamma oscillations. Neuron
abstractText  The hypocretin (Hcrt) (also known as orexin) neuropeptidic wakefulness-promoting system is implicated in the regulation of spatial memory, but its specific role and mechanisms remain poorly understood. In this study, we revealed the innervation of the medial entorhinal cortex (MEC) by Hcrt neurons in mice. Using the genetically encoded G-protein-coupled receptor activation-based Hcrt sensor, we observed a significant increase in Hcrt levels in the MEC during novel object-place exploration. We identified the function of Hcrt at presynaptic glutamatergic terminals, where it recruits fast-spiking parvalbumin-positive neurons and promotes gamma oscillations. Bidirectional manipulations of Hcrt neurons' projections from the lateral hypothalamus (LH(Hcrt)) to MEC revealed the essential role of this pathway in regulating object-place memory encoding, but not recall, through the modulation of gamma oscillations. Our findings highlight the significance of the LH(Hcrt)-MEC circuitry in supporting spatial memory and reveal a unique neural basis for the hypothalamic regulation of spatial memory.
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