Esr1+ hypothalamic-habenula neurons shape aversive states
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Nature neuroscience - 26(2023), 7 vom: 22. Juli, Seite 1245-1255 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Calvigioni, Daniela [VerfasserIn] |
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| Anmerkungen: |
Date Completed 07.07.2023 Date Revised 18.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41593-023-01367-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35850869X |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Fuzik, Janos |e verfasserin |4 aut | |
| 700 | 1 | |a Le Merre, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Slashcheva, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Ortiz, Cantin |e verfasserin |4 aut | |
| 700 | 1 | |a Lentini, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Csillag, Veronika |e verfasserin |4 aut | |
| 700 | 1 | |a Graziano, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Nikolakopoulou, Ifigeneia |e verfasserin |4 aut | |
| 700 | 1 | |a Weglage, Moritz |e verfasserin |4 aut | |
| 700 | 1 | |a Lazaridis, Iakovos |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hoseok |e verfasserin |4 aut | |
| 700 | 1 | |a Lenzi, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Hyunsoo |e verfasserin |4 aut | |
| 700 | 1 | |a Reinius, Björn |e verfasserin |4 aut | |
| 700 | 1 | |a Carlén, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Meletis, Konstantinos |e verfasserin |4 aut | |
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