A septo-hypothalamic-medullary circuit directs stress-induced analgesia
Abstract Stress is a potent modulator of pain. Specifically, acute stress due to physical restraint induces stress-induced analgesia (SIA). However, where and how acute stress and pain pathways interface in the brain are poorly understood. Here, we describe how the dorsal lateral septum (dLS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamic area (LHA) of mice. Taking advantage of transsynaptic viral-genetic, optogenetic, and chemogenetic techniques, we show that the dLS→LHA circuitry is sufficient to drive analgesia and is required for SIA. Further, our results reveal that the dLS→LHA pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the inhibitory dLS neurons are recruited specifically when the mice struggle to escape under restraint and, in turn, inhibit excitatory LHA neurons. As a result, the RVM neurons downstream of LHA are disengaged, thus suppressing nociception. Together, we delineate a poly-synaptic pathway that can transform escape behavior in mice under restraint to acute stress into analgesia..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 27. März Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Shah, Devanshi Piyush [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2023.01.30.526171 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI038584190 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI038584190 | ||
| 003 | DE-627 | ||
| 005 | 20240328090506.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230203s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2023.01.30.526171 |2 doi | |
| 035 | |a (DE-627)XBI038584190 | ||
| 035 | |a (biorXiv)10.1101/2023.01.30.526171 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Shah, Devanshi Piyush |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a A septo-hypothalamic-medullary circuit directs stress-induced analgesia |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Stress is a potent modulator of pain. Specifically, acute stress due to physical restraint induces stress-induced analgesia (SIA). However, where and how acute stress and pain pathways interface in the brain are poorly understood. Here, we describe how the dorsal lateral septum (dLS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamic area (LHA) of mice. Taking advantage of transsynaptic viral-genetic, optogenetic, and chemogenetic techniques, we show that the dLS→LHA circuitry is sufficient to drive analgesia and is required for SIA. Further, our results reveal that the dLS→LHA pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the inhibitory dLS neurons are recruited specifically when the mice struggle to escape under restraint and, in turn, inhibit excitatory LHA neurons. As a result, the RVM neurons downstream of LHA are disengaged, thus suppressing nociception. Together, we delineate a poly-synaptic pathway that can transform escape behavior in mice under restraint to acute stress into analgesia. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Sharma, Pallavi Raj |4 aut | |
| 700 | 1 | |a Agarwal, Rachit |0 (orcid)0000-0001-5703-4461 |4 aut | |
| 700 | 1 | |a Barik, Arnab |0 (orcid)0000-0001-6850-0894 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2024) vom: 27. März |
| 773 | 1 | 8 | |g year:2024 |g day:27 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2023.01.30.526171 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 27 |c 03 | ||