Basolateral Amygdala to Nucleus Accumbens Communication Differentially Mediates Devaluation Sensitivity of Sign- and Goal-Tracking Rats

Abstract

Rats rely on communication between the basolateral amygdala (BLA) and nucleus accumbens (NAc) to express lever directed approach in a Pavlovian lever autoshaping (PLA) task that distinguishes sign- and goal-tracking rats. During PLA, sign-tracking rats preferentially approach an insertable lever cue, while goal-tracking rats approach a foodcup where rewards are delivered. While sign-tracking rats inflexibly respond to cues even after the associated reward is devalued, goal-tracking rats flexibly reduce responding to cues during outcome devaluation. Here, we sought to determine whether BLA-NAc communication, which is necessary for sign, but not goal-tracking, drives a rigid appetitive approach of sign-tracking rats that are insensitive to manipulations of outcome value. Using a contralateral chemogenetic inactivation design, we injected contralateral BLA and NAc core with inhibitory DREADD (hm4Di-mCherry) or control (mCherry) constructs. To determine sign- and goal-tracking groups, we trained rats in five PLA sessions in which brief lever insertion predicts food pellet delivery. We sated rats on training pellets (devalued condition) or chow (valued condition) before systemic clozapine injections (0.1 mg/kg) to inactivate BLA and contralateral NAc during two outcome devaluation probe tests, in which we measured lever and foodcup approach. Contralateral BLA-NAc chemogenetic inactivation promoted a flexible lever approach in sign-tracking rats but disrupted the flexible foodcup approach in goal-tracking rats. Consistent with a prior BLA-NAc disconnection lesion study, we find contralateral chemogenetic inactivation of BLA and NAc core reduces lever, but not the foodcup approach in PLA. Together these findings suggest rigid appetitive associative encoding in BLA-NAc of sign-tracking rats hinders the expression of flexible behavior when outcome value changes.

Keywords: basolateral amygdala; devaluation; flexibility; goal-tracking; nucleus accumbens; sign-tracking.

Figure 1

Pavlovian lever autoshaping (PLA) acquisition data. Data represents (A) average Pavlovian Conditioned Approach (PCA) score, (B) lever contacts, (C) foodcup contacts during training; and (D) both lever and foodcup contacts on fifth training session are represented as a function of viral condition; there were no differences as a function of virus (ps > 0.05).

Figure 2

Outcome devaluation in sign- and goal-tracking rats. Data represent individual subjects (line) and group averaged (bars) for (A,B) preferred responding (ST: lever contact, GT: foodcup contact) and (C,D) non-preferred responding (ST: foodcup contact, GT: lever contact), + SEM. A priori planned comparisons reveal that (A) hM4Di (t₍₁₀₎ = 2.582, *p < 0.05), but not mCherry (t₍₈₎ = 1.495, p = 0.173), ST rats show devaluation effect (difference between valued and devalued) for lever directed behavior. (B) mCherry (t₍₉₎ = 2.273 *p < 0.05), but not hM4Di (t₍₁₁₎ = 0.270, p = 0.792), GT rats show devaluation effect for foodcup directed behavior. No interactions were observed for non-preferred responding. (E) Population distributions of devaluation difference scores (valued preferred responding–devalued preferred responding). ST hM4Di population distribution was significantly shifted above zero and significantly different than the GT hM4Di population distribution (*p < 0.05, ^#p = 0.07). (F) Consumption during the choice test following outcome devaluation is represented as a function of tracking and viral condition.

Figure 3

Lever and foodcup contact data represent individual subjects (dot) and group averages (bars) + SEM for (A) lever (B) and foodcup contacts during outcome devaluation, collapsed across Tracking Group. (C) Data represent contacts collapsed across Tracking Group and Value; basolateral amygdala (BLA)–nucleus accumbens (NAc) core inactivation disrupts lever but not foodcup approach, F_(1,34) = 4.484, p = 0.042. Post hoc tests revealed a trend toward an effect of inactivation on lever-directed responding, such that hM4Di rats pressed less than mCherry rats, t₍₂₂₎ = 2.05, ^#p = 0.053. Sex effects split by Response type (D), Tracking Group (E,G), and Virus group (F,H). Data represent group averages (bars) + SEM. (D) Females perform more lever-directed responses than males during outcome devaluation tests overall. (G) Tracking Group × Value × Sex interaction of foodcup responding (F_(1,34) = 5.02, p = 0.032). *Indiciates significant difference with p < 0.05.

Figure 4

Histological verification of viral expression in NAc core and BLA. Rats were injected with viral constructs unilaterally in BLA and in contralateral NAc core (mm from Bregma; Paxinos and Watson, 2007); scale bars represent 500 μm. Unilateral expression was counterbalanced, but the expression is shown in both hemispheres. (A) Schematic representation of viral expression and (B) representative image of mCherry (top) and hM4Di (bottom) NAc core expression. (C) Schematic representation of viral expression and (D) representative image of (top) mCherry and hM4Di (bottom) BLA expression. The legend indicates the density of overlapping expression, where (n) is the number of overlapping cases to produce the represented opacity.