New Article

Bidirectional and context-dependent changes in theta and gamma oscillatory brain activity in noradrenergic cell-specific Hypocretin/Orexin receptor 1-KO mice.

The few thousands neurons in the hypothalamus that produce the Hypocretin/Orexin neuromodulator project widely throughout the brain. The circuit they form acts a neural hub, able to integrate multimodal sensory and physiological information and tune accordingly the arousal and motivational state of the animal. Major targets of Hypocretin neurons are the pontomedullary Noradrenergic cell groups that include the locus coeruleus. The authors created mice lacking specifically this Hypocretin-to-Noradrenergic cell circuit. They found that these mice were impaired in mounting a normal arousal response when exposed to stressful conditions. Surprisingly, the same mice exhibited however enhanced markers of arousal when engaged in rewarding activities such as nest-building. Hence the works suggests that the Hypocretin-to-Noradrenaline connection functions to tune arousal up under stress, but also acts to prevent hyperarousal in some self-motivated spontaneous behaviors. This study may have clinical relevance as novel drugs acting to antagonize or mimic Hypocretin receptors are being investigated for a number of neuropsychological disorders.