Functional role of Gastrin Releasing Peptide (GRP) and GRP expressing neurons in the gustatory cortex

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PROJECT SUMMARY It is well-established that neural activity in the rodent gustatory cortex (GC) encodes taste, taste-predictive cues and taste-guided decisions. These neural signals play an important role in guiding behaviors related to taste and consumption. Recent electrophysiological and imaging studies demonstrated that GC can also process interoceptive information pertaining to the homeostatic control of feeding and drinking, with hunger/satiety and thirst/quenching affecting neural activity on both the slow time scale of ongoing activity and the fast time scale of taste- and cue-evoked activity. The GC circuits and neurochemicals involved in processing interoceptive signals as well as their role in driving specific behavioral responses are not fully understood yet. We propose to address this gap by focusing on a neuropeptide, the gastrin-releasing peptide, (GRP), and a GC population of neurons producing GRP. As GRP is a feeding-suppressing peptide, neurons expressing GRP (GRP+) are ideal candidates to sense homeostatic states and mediate the effects of GC on consumption. Our preliminary data show that GC GRP+ neurons project to the basolateral nucleus of the amygdala (BLA) – a nucleus known for its role in mediating aversive and appetitive behaviors – corroborating the idea that this population of cells may indeed control behavior and lead to meal termination. The experiments in this proposal we will test the overarching hypothesis that GC GRP+ neurons process interoceptive homeostatic signals at both the slow and fast temporal scales of ongoing and taste/cue- evoked activity, and are capable of inhibiting consumption. Anatomical and immunohistological methods, in vitro patch clamp electrophysiology, 2-photon (2P) calcium imaging in behaving mice, and optogenetic/pharmacological manipulations will be used to address the following specific aims: Aim #1 will rely on anatomical methods, patch clamp and optogenetics to establish neurochemical identity, electrophysiological properties, laminar distribution and connectivity of GC GRP+ neurons. The studies will test the hypothesis that GC GRP+ neurons are excitatory neurons sending projections to BLA and that GRP released by these neurons modulates the activity of BLA circuits. Aim #2 will use 2P calcium imaging to study the activity patterns of GRP+ and GRP- neurons in mice engaged in behavioral tasks probing taste and anticipatory-cues processing under distinct homeostatic conditions. These experiments will test the hypothesis that activity of GC GRP+ neurons, and specifically those projecting to BLA, integrate sensory signals related to nutrients (taste and cues) with homeostatic signals related to meal termination. Finally, Aim #3 will rely on optogenetic activation at different time scales to establish the behavioral contribution of GC GRP+ neurons and investigate the neurochemical bases of this effect. The experiments will test the hypothesis that GC GRP+ neurons provide a meal termination signal, and that their projection to BLA mediates, at least in part, the control of feeding behavior. Altogether, the proposed experiments will establish a new research avenue on the GC and GCBLA circuits involved in representing interoceptive signals and guiding homeostatic behaviors. If successful, these study will i) enhance our understanding of the function of the gustatory cortex; ii) unveil a new role for cortical GRP within the GRPBLA axis; iii) establish a model for studying peptidergic transmission in cortico-amygalar circuits. The results will have important consequences for our understanding of the role of GC in ingestive behaviors.