The role of the nucleus accumbens in learned approach behavior diminishes with training

Abstract

Nucleus accumbens dopamine plays a key role in reward‐directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine‐independent reward approach. In the present study, rats approached and inserted the head into a reward compartment in response to a cue signaling food delivery. On days 4 and 5 of 28‐trial‐per‐day sessions, D1 receptor antagonist R(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (SCH23390) infused to the NAc core reduced the probability and speed of cued approach. The disruptive effect of D1 receptor blockade was specific to the nucleus accumbens core and not seen with drug infusions to nearby dopamine target regions. In rats that received drug infusions after extended training (days 10 or 11), accumbens core D1 receptor blockade produced little effect on the expression of the same behavior. These results could have been due to a continued accumbens mediation of cued approach even after the behavior had become independent of accumbens D1 receptors. However, accumbens core ionotropic glutamate receptor blockade disrupted cued approach during early but not late stages of training, similar to the effects of D1 antagonist infusions. The results suggest that with extended training, a nucleus accumbens D1‐dependent behavior becomes less dependent not only on nucleus accumbens D1 transmission but also on excitatory transmission in the nucleus accumbens. These findings fill an important gap in a growing literature on reorganization of striatal function over the course of training.

Context coding in the mouse nucleus accumbens modulates motivationally-relevant information

“…To determine whether our behavioral predictive power was arbitrary to any population-level component, we ran the binomial regression on all major components, and found that only those containing significant context information had predictive utility during the delay period. These population-level results align with a growing body of work advocating for population-level interpretations of neural data, suggesting that certain neural computations are better understood in terms of their population-level versus single-unit output (Ebitz & Hayden, 2021;Gallego et al, 2017;Saxena & Cunningham, 2019;Vyas et al, 2020). A primary argument for this approach is that there is a high degree of correlation and redundancy across single-unit coding, suggesting that the large neural space occupied by units in a region can be captured by a drastically lower dimensional latent space.…”

“…However, speculatively this finding may suggest that during initial learning, the NAc receives cue information and processes it solely in terms of its motivational relevance, and some other structure is supporting context-dependent behavior, but then after extensive learning, it forms representations of the associative structure. Interestingly, recent work has suggested that motivated approach behavior becomes less NAc-dependent as training progresses (Dobrovitsky et al, 2019). Whether or not this is related to a shift in the role of the NAc as a behavior becomes learned, or related to distinct inputs such as from the hippocampus and cortex, remains to be determined.…”

Context coding in the mouse nucleus accumbens modulates motivationally relevant information

“…However, speculatively this finding may suggest that during initial learning, the NAc receives cue information and processes it solely in terms of its motivational relevance, and some other structure is supporting context-dependent behavior, but then after extensive learning, it forms representations of the associative structure. Interestingly, recent work has suggested that motivated approach behavior becomes less NAc dependent as training progresses [ 63 ]. Whether or not this is related to a shift in the role of the NAc as a behavior becomes learned, or related to distinct inputs such as from the hippocampus and cortex, remains to be determined.…”

NMDA receptor-dependent plasticity in the nucleus accumbens connects reward-predictive cues to approach responses

“…However, the dependence of S+-evoked excitation and behavioral performance on NMDARs was absent in overtrained animals (Fig. 4), suggesting that overtraining induces a secondary plastic change within the NAc core 47 (stage 4, Fig. 9).…”