Activation of Glutamatergic Fibers in the Anterior NAc Shell Modulates Reward Activity in the aNAcSh, the Lateral Hypothalamus, and Medial Prefrontal Cortex and Transiently Stops Feeding

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Abstract
Although the release of mesoaccumbal dopamine is certainly involved in rewarding responses, recent studies point to the importance of the interaction between it and glutamate. One important component of this network is the anterior nucleus accumbens shell (aNAcSh), which sends GABAergic projections into the lateral hypothalamus (LH) and receives extensive glutamatergic inputs from, among others, the medial prefrontal cortex (mPFC). The effects of glutamatergic activation of aNAcSh on the ingestion of rewarding stimuli as well as its effect in the LH and mPFC are not well understood. Therefore, we studied behaving mice that express a light-gated channel (ChR2) in glutamatergic fibers in their aNAcSh while recording from neurons in the aNAcSh, or mPFC or LH. In Thy1-ChR2, but not wild-type, mice activation of aNAcSh fibers transiently stopped the mice licking for sucrose or an empty sipper. Stimulation of aNAcSh fibers both activated and inhibited single-unit responses aNAcSh, mPFC, and LH, in a manner that maintains firing rate homeostasis. One population of licking-inhibited pMSNs in the aNAcSh was also activated by optical stimulation, suggesting their relevance in the cessation of feeding. A rewarding aspect of stimulation of glutamatergic inputs was found when the Thy1-ChR2 mice learned to nose-poke to self-stimulate these inputs, indicating that bulky stimulation of these fibers are rewarding in the sense of wanting. Stimulation of excitatory afferents evoked both monosynaptic and polysynaptic responses distributed in the three recorded areas. In summary, we found that activation of glutamatergic aNAcSh fibers is both rewarding and transiently inhibits feeding.SIGNIFICANCE STATEMENTWe have established that the activation of glutamatergic fibers in the anterior nucleus accumbens shell (aNAcSh) transiently stops feeding and yet, because mice self-stimulate, is rewarding in the sense of wanting. Moreover, we have characterized single-unit responses of distributed components of a hedonic network (comprising the aNAcSh, medial prefrontal cortex, and lateral hypothalamus) recruited by activation of glutamatergic aNAcSh afferents that are involved in encoding a positive valence signal important for the wanting of a reward and that transiently stops ongoing consummatory actions, such as licking.

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