Dr. Hector Horacio Sagarnaga Muñoz

Experiencia

Feedforward inhibition of stress by brainstem neuropeptide Y neurons Yan Zhang 1,2,3,13, Jiayi Shen4,13, Famin Xie 1 , Zhiwei Liu4 , Fangfang Yin5 Mingxiu Cheng6,7, Liang Wang 4 , Meiting Cai3 , Herbert Herzog8,9, Ping Wu5 Zhi Zhang 1 , Cheng Zhan 3,4 & Tiemin Liu 1,2,10,11,12 Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initi- ating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously unchar- acterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice. NPYDRN/vlPAG neurons are rapidly activated by various stressful sti- muli. Inhibiting these neurons exacerbated hypophagic and anxiety responses during stress, while activation significantly ameliorates acute stress-induced hypophagia and anxiety levels and transmits positive valence. Furthermore, NPYDRN/vlPAG neurons exert differential but synergic anxiolytic effects via inhibi- tory projections to the paraventricular thalamic nucleus (PVT) and the lateral hypothalamic area (LH). Together, our findings reveal a feedforward inhibition neural mechanism underlying stress resistance and suggest NPYDRN/vlPAG neurons as a potential therapeutic target for stress-related disorders. Stress affects the physiological functions and behaviors of individuals, yielding both positive and negative outcomes. On the positive side, stressors trigger the fight and flight response that is crucial to the performance and survival under threats1 . On the negative side, impaired adaptation and resistance to stressful events can precipitate the onset or relapse of symptoms in a range of psychiatric and beha- vioral disorders, including anxiety2 , depression3 , hyperphagia4 or hypophagia5 , and even posttraumatic stress disorder (PTSD)6 a

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