Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.
Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and maladaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors. Here, we demonstrate that Dyn cells are broadly activated by threats and release Dyn locally in the vmPFC to limit passive defensive behaviors. We further demonstrate that vmPFC Dyn-mediated signaling promotes a switch of vmPFC networks to a fear-related state. In conclusion, we reveal a previously unknown role of vmPFC Dyn neurons and Dyn neuropeptidergic transmission in suppressing defensive behaviors in response to threats via state-driven changes in vmPFC networks.
Pubmed ID: 38614102 RIS Download
Research resources used in this publication
- pGP-AAV-syn-jGCaMP7f-WPRE (RRID:Addgene_104488) (plasmid)
- pGP-AAV-syn-FLEX-jGCaMP7f-WPRE (RRID:Addgene_104492) (plasmid)
- pAAV-Ef1a-DIO EYFP (RRID:Addgene_27056) (plasmid)
- B6J.Cg-Ssttm3.1(flpo)Zjh/AreckJ (RRID:IMSR_JAX:031629) (organism)
- B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J (RRID:IMSR_JAX:007914) (organism)
- B6;129S-Pdyntm1.1(cre)Mjkr/LowlJ (RRID:IMSR_JAX:027958) (organism)
- C57BL/6J (RRID:IMSR_JAX:000664) (organism)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Goat Anti-Chicken IgY H&L (Alexa Fluor® 488) preadsorbed (RRID:AB_2827653)
- Alexa Fluor 594-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Shp Sr Prot) (RRID:AB_2340689)
- Anti-Somatostatin Antibody, clone YC7 (RRID:AB_2255365)
- Alexa Fluor 594-AffiniPure Donkey Anti-Guinea Pig IgG (H+L) (min X Bov,Ck,Gt,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (RRID:AB_2340474)
- Alexa Fluor 488-AffiniPure Donkey Anti-Guinea Pig IgG (H+L) (min X Bov,Ck,Gt,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (RRID:AB_2340472)
- Anti-GFP antibody (RRID:AB_300798)
- ProDynorphin antibody (RRID:AB_297019)
Associated grants
- Agency: Intramural NIH HHS, United States
Id: ZIA MH002970
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This is a list of tools and resources that we have found mentioned in this publication.
Goat Anti-Chicken IgY H&L (Alexa Fluor® 488) preadsorbed (antibody)
RRID:AB_2827653
This polyclonal targets IgY H&L
View all literature mentionsAlexa Fluor 594-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Shp Sr Prot) (antibody)
RRID:AB_2340689
This unknown targets Rat IgG (H+L)
View all literature mentionsAnti-Somatostatin Antibody, clone YC7 (antibody)
RRID:AB_2255365
This monoclonal targets Somatostatin
View all literature mentionsAlexa Fluor 594-AffiniPure Donkey Anti-Guinea Pig IgG (H+L) (min X Bov,Ck,Gt,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (antibody)
RRID:AB_2340474
This unknown targets Guinea Pig IgG (H+L)
View all literature mentionsAlexa Fluor 488-AffiniPure Donkey Anti-Guinea Pig IgG (H+L) (min X Bov,Ck,Gt,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (antibody)
RRID:AB_2340472
This polyclonal targets Guinea pig
View all literature mentionsAnti-GFP antibody (antibody)
RRID:AB_300798
This polyclonal targets GFP
View all literature mentionsProDynorphin antibody (antibody)
RRID:AB_297019
This polyclonal targets ProDynorphin
View all literature mentionsB6J.Cg-Ssttm3.1(flpo)Zjh/AreckJ (organism)
RRID:IMSR_JAX:031629
Mus musculus with name B6J.Cg-Ssttm3.1(flpo)Zjh/AreckJ from IMSR.
View all literature mentionsB6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J (organism)
RRID:IMSR_JAX:007914
Mus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsB6;129S-Pdyntm1.1(cre)Mjkr/LowlJ (organism)
RRID:IMSR_JAX:027958
Mus musculus with name B6;129S-Pdyntm1.1(cre)Mjkr/LowlJ from IMSR.
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentions
