TUBEROMAMMILLARY NUCLEUS HISTAMINERGIC NEURONS UNDERLIE SUSCEPTIBILITY AND RESILIENCE TO PSYCHOSOCIAL STRESS

Psychosocial stress is considered a severe pathogenic factor of psychiatric disorders, characterized by dysfunctions of cognitive, emotional, and social domains. Histaminergic (HA) neurons of the tuberomamillary nucleus (TMNHA) are required to control these behavioural domains, being critically involved in modulating the effects of protective agents against stress-induced maladaptive consequences. Importantly, not everyone who experiences an adverse or stressful event succumbs to negative outcomes and enters a pathological state. Indeed, some individuals are highly vulnerable to the pathological consequences of stress exposure, whereas others appear to be resilient. However, whether TMNHA neurons are engaged in the initial response or in more durable resilience/susceptibility responses remains poorly understood. To disentangle the involvement of the HA neurons in stress susceptibility and resilience, chemogenetic, pharmacological and genetic manipulations techniques were used in a murine model of social defeat stress (SDS). We showed that manipulation of HA neurons impacts on the instatement of a specific stress-induced phenotype. Activation of TMNHA neurons promotes resilience to the SDS-induced behavioural alterations, whereas inhibition of these neurons triggers susceptibility. The results obtained revealed the full implication of the brain HA system in promoting a coping behaviour toward stress-related dysfunctions. This suggests that interventions targeting HA system can promote coping and long-term resilience and ultimately normalizing the affected systems.