• Activation of the Rostral Intralaminar Thalamus Drives Reinforcement through Striatal Dopamine Release

      Cover, K.K.; Gyawali, U.; Kerkhoff, W.G. (Elsevier B.V., 2019)
      Glutamatergic projections of the thalamic rostral intralaminar nuclei of the thalamus (rILN) innervate the dorsal striatum (DS) and are implicated in dopamine (DA)-dependent incubation of drug seeking. However, the mechanism by which rILN signaling modulates reward seeking and striatal DA release is unknown. We find that activation of rILN inputs to the DS drives cholinergic interneuron burst-firing behavior and DA D2 receptor-dependent post-burst pauses in cholinergic interneuron firing. In vivo, optogenetic activation of this pathway drives reinforcement in a DA D1 receptor-dependent manner, and chemogenetic suppression of the rILN reduces dopaminergic nigrostriatal terminal activity as measured by fiber photometry. Altogether, these data provide evidence that the rILN activates striatal cholinergic interneurons to enhance the pursuit of reward through local striatal DA release and introduce an additional level of complexity in our understanding of striatal DA signaling. © 2019 The Authors
    • Basolateral Amygdala to Nucleus Accumbens Communication Differentially Mediates Devaluation Sensitivity of Sign- and Goal-Tracking Rats

      Kochli, D.E.; Keefer, S.E.; Gyawali, U.; Calu, D.J. (Frontiers Media S.A., 2020-11-25)
      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. Copyright Copyright Copyright 2020 Kochli, Keefer, Gyawali and Calu.