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      A quadruple dissociation of reward-related behaviour in mice across excitatory inputs to the nucleus accumbens shell

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          Abstract

          The nucleus accumbens shell (NAcSh) is critically important for reward valuations, yet it remains unclear how valuation information is integrated in this region to drive behaviour during reinforcement learning. Using an optogenetic spatial self-stimulation task in mice, here we show that contingent activation of different excitatory inputs to the NAcSh change expression of different reward-related behaviours. Our data indicate that medial prefrontal inputs support place preference via repeated actions, ventral hippocampal inputs consistently promote place preferences, basolateral amygdala inputs produce modest place preferences but as a byproduct of increased sensitivity to time investments, and paraventricular inputs reduce place preferences yet do not produce full avoidance behaviour. These findings suggest that each excitatory input provides distinct information to the NAcSh, and we propose that this reflects the reinforcement of different credit assignment functions. Our finding of a quadruple dissociation of NAcSh input-specific behaviours provides insights into how types of information carried by distinct inputs to the NAcSh could be integrated to help drive reinforcement learning and situationally appropriate behavioural responses.

          Abstract

          An optogenetic, spatial self-stimulation task in mice reveals how information carried by distinct inputs to the nucleus accumbens shell is potentially integrated to drive behavioural responses.

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          Most cited references85

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          Are the dorsal and ventral hippocampus functionally distinct structures?

          One literature treats the hippocampus as a purely cognitive structure involved in memory; another treats it as a regulator of emotion whose dysfunction leads to psychopathology. We review behavioral, anatomical, and gene expression studies that together support a functional segmentation into three hippocampal compartments: dorsal, intermediate, and ventral. The dorsal hippocampus, which corresponds to the posterior hippocampus in primates, performs primarily cognitive functions. The ventral (anterior in primates) relates to stress, emotion, and affect. Strikingly, gene expression in the dorsal hippocampus correlates with cortical regions involved in information processing, while genes expressed in the ventral hippocampus correlate with regions involved in emotion and stress (amygdala and hypothalamus).
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            The role of medial prefrontal cortex in memory and decision making.

            Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Amygdala circuitry mediating reversible and bidirectional control of anxiety.

              Anxiety--a sustained state of heightened apprehension in the absence of immediate threat--becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)--achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA--exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA-CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.
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                Author and article information

                Contributors
                tmhomas@umn.edu
                Journal
                Commun Biol
                Commun Biol
                Communications Biology
                Nature Publishing Group UK (London )
                2399-3642
                30 January 2023
                30 January 2023
                2023
                : 6
                : 119
                Affiliations
                [1 ]GRID grid.17635.36, ISNI 0000000419368657, Department of Neuroscience, , University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, ; Minneapolis, MN 55455 USA
                [2 ]GRID grid.17635.36, ISNI 0000000419368657, Medical Discovery Team on Addiction, University of Minnesota, 3-432 McGuire Translational Research Facility, 2001 6th St SE, ; Minneapolis, MN 55455 USA
                [3 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Department of Psychiatry, , Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, ; New York, NY 10029 USA
                [4 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Rehabilitation Medicine Research Center, Department of Physical Medicine and Rehabilitation, Mayo Clinic, 200 First St SW, ; Rochester, MN 55905 USA
                Author information
                http://orcid.org/0000-0003-2198-9922
                http://orcid.org/0000-0002-2123-5824
                http://orcid.org/0000-0003-3644-9072
                http://orcid.org/0000-0001-5721-5350
                Article
                4429
                10.1038/s42003-023-04429-6
                9886947
                36717646
                1d3ed250-af7a-41be-b5b5-636e5088b9c8
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 March 2021
                : 5 January 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000026, U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA);
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award ID: R01 DA019666
                Award ID: R01 DA041808
                Award ID: K02 DA035459
                Award ID: P30 DA048742
                Award Recipient :
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: Breyer-Longden Family Foundation
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
                Categories
                Article
                Custom metadata
                © The Author(s) 2023

                neural circuits,reward,motivation
                neural circuits, reward, motivation

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