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      Intrinsic Excitability in Layer IV–VI Anterior Insula to Basolateral Amygdala Projection Neurons Correlates with the Confidence of Taste Valence Encoding


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          Avoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. However, the perceived valence of sensory information can change following conflicting experiences. Pleasurability and aversiveness are two crucial parameters defining the perceived valence of a taste and can be impacted by novelty. Importantly, the ability of a given taste to serve as the conditioned stimulus (CS) in conditioned taste aversion (CTA) is dependent on its valence. Activity in anterior insula (aIC) Layer IV–VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlated with and necessary for CTA learning and retrieval, as well as the expression of neophobia toward novel tastants, but not learning taste familiarity. Yet, the cellular mechanisms underlying the updating of taste valence representation in this specific pathway are poorly understood. Here, using retrograde viral tracing and whole-cell patch-clamp electrophysiology in trained mice, we demonstrate that the intrinsic properties of deep-lying Layer IV–VI, but not superficial Layer I–III aIC-BLA neurons, are differentially modulated by both novelty and valence, reflecting the subjective predictability of taste valence arising from prior experience. These correlative changes in the profile of intrinsic properties of LIV–VI aIC-BLA neurons were detectable following both simple taste experiences, as well as following memory retrieval, extinction learning, and reinstatement.

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              Intuition suggests that perception follows sensation and therefore bodily feelings originate in the body. However, recent evidence goes against this logic: interoceptive experience may largely reflect limbic predictions about the expected state of the body that are constrained by ascending visceral sensations. In this Opinion article, we introduce the Embodied Predictive Interoception Coding model, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions. We then discuss how disruptions in interoceptive predictions could function as a common vulnerability for mental and physical illness.

                Author and article information

                Society for Neuroscience
                9 December 2022
                17 January 2023
                January 2023
                : 10
                : 1
                : ENEURO.0302-22.2022
                [1] 1Sagol Department of Neurobiology, University of Haifa , Abba Khoushy Ave 199, Haifa, 3498838, Israel
                [2] 2Center for Gene Manipulation in the Brain, University of Haifa , Haifa, Israel
                [3] 3Institute of Biochemistry and Molecular Medicine, University of Bern , Bühlstrasse 28, 3012 Bern, Switzerland
                Author notes

                The authors declare no competing financial interests.

                Author contributions: S.K.C., A.Y., and K.R. designed research; S.K.C., A.Y., H.K., R.S., F.C., and M.K. performed research; S.K.C., A.Y., R.S., F.C., L.M., S.S., and K.R. analyzed data; S.K.C., A.Y., and K.R. wrote the paper.

                This research was supported by Israel Science Foundation (ISF) Grants ISF 946/17 and ISF 258/20 (to K.R.).


                S.K.C. and A.Y. contributed equally to this work.

                Correspondence should be addressed to Kobi Rosenblum at kobir@ 123456psy.haifa.ac.il or Adonis Yiannakas at adonis.yiannakas@ 123456gmail.com or Sailendrakumar Kolatt Chandran at sailendrakumarkc@ 123456gmail.com .
                Author information
                Copyright © 2023 Kolatt Chandran et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                : 24 July 2022
                : 1 September 2022
                : 11 September 2022
                Page count
                Figures: 6, Tables: 5, Equations: 0, References: 127, Pages: 39, Words: 00
                Funded by: Israel Science Foundation (ISF), doi 10.13039/501100003977;
                Award ID: 258/20
                Research Article: Confirmation
                Cognition and Behavior
                Custom metadata
                January 2023

                association,insula,intrinsic properties,novel,salience,taste
                association, insula, intrinsic properties, novel, salience, taste


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