Journal: bioRxiv
Article Title: Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors
doi: 10.1101/2023.02.23.529717
Figure Lengend Snippet: Chemogenetic activation of CRF+ BNST neurons decreased lever pressing for sucrose pellets in high-performing males. ( A ) 6–7-week-old CRF-ires-Cre transgenic mice were bilaterally injected with Cre-dependent Gq-DREADD or a control Cre-dependent mCherry virus. After recovery, mice were fasted and trained in operant chambers to lever press for sucrose pellets. Over 10 days, a progressive ratio (PR) baseline frequency of lever pressing was collected, wherein mice were trained to lever press at increasing frequencies in an (FR(n+1) x 15) PR reinforcement schedule. During PR/concurrent chow (CHOW) baseline training, concurrently available lab chow was freely available on the chamber floor. Mice were then refed and allowed ad libitum access to lab chow for 20 hours, and sucrose pellets for 4 hours, prior to an outcome devaluation trial. During 4 days of PR/CHOW testing, mice were injected with alternating treatments of CNO or Vehicle 30 minutes prior to PR/CHOW testing, to assess how chemogenetic activation of CRF+ BNST neurons alters lever pressing in the PR/CHOW task. Appetite was assessed over two days of free feed testing, wherein mice were injected with alternating treatments of CNO or Vehicle. During open field and sucrose preference testing, all mice were injected with CNO solution. Mice were fasted to 85-90% of their ad libitum body weights throughout training and testing, except where marked with a chow icon, which represents free access to standard lab chow. Arrows represent daily CNO or Vehicle injections, 30 minutes prior to testing. ( B ) Males (grey) lever pressed significantly more frequently than females (black) during PR baseline training ( p < 0.05) on days 2, 4, 5, 7, 8 ( p < 0.05), and 10 ( p < 0.01). ( C ) Males also pressed more than females during PR/CHOW ( p < 0.001) baseline training, including days 1 ( p < 0.05), 2 ( p < 0.001), and 3-5 ( p < 0.01). ( D ) Males lever pressed significantly less when re-fed during outcome devaluation, compared to PR ( p < 0.001) or PR/CHOW ( p < 0.0001) baseline. Female lever pressing did not significantly decline during outcome devaluation. ( E ) Mice were designated high performers if their average PR/CHOW baseline lever pressing was greater than the median lever pressing (perforated line) for all mice. All high-performing mice were males (gray points), but all females (black points) were at or below the median baseline frequency. ( F ) In the PR/Chow test, high-performing Gq-DREADD males, when injected with CNO, lever pressed less than when injected with Vehicle ( p < 0.05). No effect of CNO was observed in mCherry control mice ( p = 0.884). Values are plotted as individual values and mean +/- SEM. * p < 0.05; *** p < 0.001.
Article Snippet: Standard mouse operant chambers (Med Associates, Fairfax, VT) were housed in sound-attenuating cubicles inside a behavioral testing room.
Techniques: Activation Assay, Transgenic Assay, Injection