| First Author | Calvigioni D | Year | 2023 |
| Journal | Nat Neurosci | Volume | 26 |
| Issue | 7 | Pages | 1245-1255 |
| PubMed ID | 37349481 | Mgi Jnum | J:353886 |
| Mgi Id | MGI:7715052 | Doi | 10.1038/s41593-023-01367-8 |
| Citation | Calvigioni D, et al. (2023) Esr1(+) hypothalamic-habenula neurons shape aversive states. Nat Neurosci 26(7):1245-1255 |
| abstractText | Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles and projection patterns. We found that genetically defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors, such as estrogen receptor 1-expressing (Esr1(+)) LHA-LHb neurons induce aversion, whereas neuropeptide Y-expressing (Npy(+)) LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1(+) LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive signals in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1(+) LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types and provide evidence for the role of Esr1(+) neurons in aversion and sexually dimorphic stress sensitivity. |
