Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice

Objective To explore the regulatory effects of hypocretin (Hcrt) neurons in lateral hypothalamus (LHHcrt)-medial entorhinal cortex (MEC) circuit on spatial memory. Methods The activity pattern of Hcrt neurons in spatial memory was recorded using in vivo fiber photometry.The morphological characteristics of connections between the Hcrt neurons and MEC neurons were identified with retrograde nerve tracer technique.Chemogenetics and optogenetics were subsequently adopted to confirm the effects of LHHcrt-MEC pathway on spatial memory. Results The optical fiber recording showed high levels of activation of Hcrt neurons during the spatial memory-related behaviors (P < 0.01).The retrograde neural tracer test indicated that Hcrt neurons were projected to MEC which was associated with spatial memory, and those projected Hcrt neurons were confirmed being activated in spatial memory.Inhibition of the LHHcrt-MEC pathway by chemogenetics significantly prolonged the latency of mice to find the correct spatial location of food (P < 0.05), and increased the number of errors in the process of finding food (P < 0.05).However, photoactivation of the LHHcrt-MEC pathway by optogenetics remarkably reduced the latency of mice to find the food location at the initial training blocks (P < 0.05). Conclusion Hcrt neurons are involved in spatial memory, and those Hcrt neurons projected from LH to the shallow layer of MEC are activated in spatial memory.Chemogenetic inhibition of the LHHcrt-MEC pathway impairs spatial memory, while optogenetic activation of this pathway enhances the function.