| First Author | Xu X | Year | 2024 |
| Journal | Curr Biol | Volume | 34 |
| Issue | 2 | Pages | 389-402.e5 |
| PubMed ID | 38215742 | Mgi Jnum | J:350888 |
| Mgi Id | MGI:7581740 | Doi | 10.1016/j.cub.2023.12.046 |
| Citation | Xu X, et al. (2024) Hypothalamic CRF neurons facilitate brain reward function. Curr Biol 34(2):389-402.e5 |
| abstractText | Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVN(CRF) neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVN(CRF) neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVN(CRF) neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVN(CRF) cell bodies, self-stimulation of PVN(CRF)-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVN(CRF)-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVN(CRF) neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVN(CRF) neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli. |
