Hadamitzky, M. | bioRxiv Science

bioRxiv2025

Constitutive activity of the inhibitory G protein pathway mediated by non-visual opsin Opn7b reduces cFos activity in stress and fear circuits and modulates avoidance behavior

Constitutive activity of G protein-coupled receptors (GPCRs) plays an important role in brain function and disease including neurodegenerative and psychiatric disorders. The non-visual opsin Opn7b is a constitutively active Gi/o coupled GPCR which has been used to synchronize neuronal networks. Here we show that expression of Opn7b in the bed nucleus of the stria terminalis and the ventral tegmental area, two interconnected brain areas involved in modulating fear and stress responses, reduces the number of cFos positive neurons and modulates avoidance behavior in mice. Thus, by constitutively activating the Gi/o pathway Opn7b can be used as a tool to reduce cFos expression and to link cFos-expressing neurons to network- and pathway-specific behavior.

neuroscience↗

bioRxiv2025

Sustained learned immunosuppression could not prevent local allergic ear swelling in a rat model of contact hypersensitivity

Taste-immune associative learning has been shown to mimic immunopharmacological responses. Conditioned pharmacological effects may therefore be considered as controlled drug dose reduction strategy to maintain treatment efficacy. Against this background, the present study applied an established taste-immune associative learning protocol to a rat model of hapten-induced contact hypersensitivity. After repeated pairings of a saccharin taste (conditioned stimulus, CS) with injections of the immunosuppressant cyclosporine A (CsA, unconditioned stimulus, UCS), animals were sensitized with the hapten. Retrieval started by presenting the CS together with sub-effective doses of CsA. This procedure preserved a conditioned suppression of splenic cytokine production. Compared to full dose treated animals, conditioned effects were neither observed in draining lymph nodes nor did it prevent ear swelling. These findings suggest that local allergic reactions in sensitized animals were most likely too strong to be responsive to the learned immunosuppressive effects. Additionally, symptoms such as itch may be more suited as readout parameter since it better reflects patients disease burden. The present study reaffirms that learned immunopharmacological effects can be preserved using a memory-updating approach. It also emphasizes the need to further explore the usability of associative learning protocols in clinical contexts in order to address disease-specific symptoms more effectively.

animal behavior and cognition↗