ABSTRACT
Consolation is a complex empathic behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects some simple form of empathy, the relationship between stress and consolation remains largely understudied. Using monogamous mandarin voles, we found that an acute restraint stress exposure significantly reduced consolation-like behaviors and induced anxiety-like behaviors. Along with these behavioral changes, corticotropin-releasing factor (CRF) and CRF receptor 1 (CRFR1) neurons were activated within the anterior cingulate cortex (ACC) and prelimbic cortex (PrL) but not within the infralimbic cortex (IL). Chemogenetic activation of CRF neurons in the ACC and PrL, recaptured acute stress-induced behavioral dysfunctions. We further observed that intracellular PKA and PKC signaling pathways mediate CRF-induced behavioral dysfunctions, but they work in a regional-specific, sex-biased manner. Together, these results suggest that the local CRF-CRFR1 system within the ACC and PrL is involved in the consolation deficits and anxiety induced by acute stress.
Subject(s)
Arvicolinae , Corticotropin-Releasing Hormone , Stress, Psychological , Animals , Arvicolinae/metabolism , Corticotropin-Releasing Hormone/metabolism , Gyrus Cinguli/metabolism , Prefrontal Cortex/metabolism , Receptors, Corticotropin-Releasing Hormone/metabolismABSTRACT
Consolation is a common response to the distress of others in humans and some social animals, but the neural mechanisms underlying this behavior are not well characterized. By using socially monogamous mandarin voles, we found that optogenetic or chemogenetic inhibition of 5-HTergic neurons in the dorsal raphe nucleus (DR) or optogenetic inhibition of serotonin (5-HT) terminals in the anterior cingulate cortex (ACC) significantly decreased allogrooming time in the consolation test and reduced sociability in the three-chamber test. The release of 5-HT within the ACC and the activity of DR neurons were significantly increased during allogrooming, sniffing, and social approaching. Finally, we found that the activation of 5-HT1A receptors in the ACC was sufficient to reverse consolation and sociability deficits induced by the chemogenetic inhibition of 5-HTergic neurons in the DR. Our study provided the first direct evidence that DR-ACC 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability.
Subject(s)
Behavior, Animal , Dorsal Raphe Nucleus/physiology , Gyrus Cinguli/physiology , Serotonergic Neurons/physiology , Serotonin/metabolism , Social Behavior , Animals , Arvicolinae , Dorsal Raphe Nucleus/metabolism , Female , Grooming , Gyrus Cinguli/metabolism , Male , Motor Activity , Neural Pathways/metabolism , Neural Pathways/physiology , Optogenetics , Receptor, Serotonin, 5-HT1A/metabolism , Serotonergic Neurons/metabolism , Time FactorsABSTRACT
Atherosclerosis, the major cause of cardiovascular diseases, has been a leading contributor to morbidity and mortality in the United States and it has been on the rise globally. Endothelial cell-cell junctions are critical for vascular integrity and maintenance of vascular function. Endothelial cell junctions dysfunction is the onset step of future coronary events and coronary artery disease.
