Figure - available from: Scientific Reports
This content is subject to copyright. Terms and conditions apply.
Experimental methods. (A) Experimental design of the cued response inhibition task (CRIT). Sessions begin with simultaneous presentation of an inhibit action cue (variable time 5–30 s), and an action cue which remained lit for 10 s following cessation of the inhibit action cue. Created with Biorender.com. (B) Schematic of chemogenetic methods. DREADDs receptors were expressed in DMS projecting OFC neurons by injecting CAV/2 Cre (green) bilaterally in the DMS and inhibitory DREADDs receptors (red) in the OFC. (C) Robust expression of both viruses in their respective brain regions is observed. (D) Administration of CNO (10 mg/kg) suppresses firing rate (Z-scored) in a spontaneously active population of OFC neurons (not limited to DREADDs expressing units) under isoflurane anesthesia. (E) Compared to saline control (light grey), CNO injection (dark grey) produced a significant and sustained modulation of OFC firing rate.
Source publication
Adolescence is characterized by increased impulsive and risk-taking behaviors. To better understand the neural networks that subserves impulsivity in adolescents, we used a reward-guided behavioral model that quantifies age differences in impulsive actions in adult and adolescent rats of both sexes. Using chemogenetics, we identified orbitofrontal...
Citations
... Optogenetic stimulation of the OFC-striatum pathway was able to reverse deficits in response inhibition in a rodent model of compulsive behavior (Burguière et al., 2013). Lastly, inhibition of OFC neurons that project to the DMS results in increased premature actions during CRIT performance (McCane et al., 2024). ...
... Adolescents and adults were food restricted, habituated to the operant box and trained to nose poke in response to a light cue for a sucrose pellet (45 mg, Bio-Serv) on a fixed ratio one schedule over two days. After successful acquisition of cue-action responding, all animals begin CRIT training as described previously (Simon et al., 2013;McCane et al., 2024). Each CRIT session lasted 60 minutes. ...
... Here we used a voluntary (Holgate et al., 2017) and relatively brief drinking paradigm in adolescents. We focused on the OFC and DMS because these regions undergo pronounced development during adolescence and are reported to mediate response inhibition and impulsive choice (Chudasama et al., 2003;Rieger et al., 2003;Eagle et al., 2007;Mar et al., 2011;McCane et al., 2024). Cortical-striatal circuitry is also implicated in in AUD pathology in clinical populations (Cservenka and Nagel, 2012;Courtney et al., 2013;Cservenka et al., 2014). ...
Alcohol use disorder (AUD) is strongly associated with initiation of drinking during adolescence. Little is known about neural mechanisms that produce the long-term detrimental effects of adolescent drinking. A critical feature of AUD is deficits in response inhibition, or the ability to withhold a reward-seeking response. Here we sought to determine if adolescent drinking affects response inhibition and encoding of neural events by the orbitofrontal cortex (OFC) and dorsomedial striatum (DMS), two regions critical for expression of response inhibition. Adolescent male and female rats were given access to alcohol for four hours a day for five consecutive days. Then, rats were tested in a cued response inhibition task as adolescents or adults while we recorded concomitantly from the OFC and DMS. Adolescent voluntary alcohol drinking impaired response inhibition and increased alcohol drinking in adult male but not female rats. Adolescent alcohol drinking also resulted in sex-specific effects on both unit firing and local field potential measures in the OFC and DMS during premature and correct actions. Collectively, these data suggest sex-specific effects of adolescent alcohol drinking on response inhibition and corresponding alterations in cortical-striatal circuitry.
Highlights
Moderate adolescent alcohol drinking disrupts adult response inhibition
Action encoding in the OFC and DMS changes after adolescent alcohol drinking
OFC-DMS connectivity is altered in males after adolescent alcohol drinking
Adolescent alcohol drinking promotes increased alcohol intake in adult males
