Cortico-Striatal Control over Adaptive Goal-Directed Responding Elicited by Cues Signaling Sucrose Reward or Punishment
Bibliographic record
Abstract
The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been associated with the expression of adaptive and maladaptive behavior elicited by fear-related and drug-associated cues. However, reported effects of mPFC manipulations on cue-elicited natural reward-seeking and inhibition thereof have been varied, with few studies examining cortico-striatal contributions in tasks that require adaptive responding to cues signaling reward and punishment within the same session. The current study aimed to better elucidate the role of mPFC and NAc subdivisions, and their functional connectivity in cue-elicited adaptive responding using a novel discriminative cue responding task. Male Long–Evans rats learned to lever-press on a VR5 schedule for a discriminative cue signaling reward, and to avoid pressing the same lever in the presence of another cue signaling punishment. Postacquisition, prelimbic (PL) and infralimbic (IL) areas of the mPFC, NAc core, shell, PL-core, or IL-shell circuits were pharmacologically or chemogenetically inhibited while animals performed under (1) nonreinforced (extinction) conditions, where the appetitive and aversive cues were presented in alternating trials alone or as a compound stimulus; and (2) reinforced conditions, whereby cued responding was accompanied by associated outcomes. PL and IL inactivation attenuated nonreinforced and reinforced goal-directed cue responding, whereas NAc core and shell inactivation impaired nonreinforced responding for the appetitive, but not aversive cue. Furthermore, PL-core and IL-shell inhibition disinhibited nonreinforced but not reinforced cue responding. Our findings implicate the mPFC as a site of confluence of motivationally significant cues and outcomes, and in the regulation of nonreinforced cue responding via downstream NAc targets. SIGNIFICANCE STATEMENT The ability to discriminate and respond appropriately to environmental cues that signal availability of reward or punishment is essential for survival. The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been implicated in adaptive and maladaptive behavior elicited by fear-related and drug-associated cues. However, less is known about the role they play in orchestrating adaptive responses to natural reward and punishment cues within the same behavioral task. Here, using a novel discriminative cue responding task combined with pharmacological or chemogenetic inhibition of mPFC, NAc and mPFC-NAc circuits, we report that mPFC is critically involved in responding to changing cued response-outcomes, both when the responses are reinforced, and nonreinforced. Furthermore, the mPFC coordinates nonreinforced discriminative cue responding by suppressing inappropriate responding via downstream NAc targets.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".