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      Basolateral and central amygdala differentially recruit and maintain dorsolateral striatum-dependent cocaine-seeking habits

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          Abstract

          In the development of addiction, drug seeking becomes habitual and controlled by drug-associated cues, and the neural locus of control over behaviour shifts from the ventral to the dorsolateral striatum. The neural mechanisms underlying this functional transition from recreational drug use to drug-seeking habits are unknown. Here we combined functional disconnections and electrophysiological recordings of the amygdalo-striatal networks in rats trained to seek cocaine to demonstrate that functional shifts within the striatum are driven by transitions from the basolateral (BLA) to the central (CeN) amygdala. Thus, while the recruitment of dorsolateral striatum dopamine-dependent control over cocaine seeking is triggered by the BLA, its long-term maintenance depends instead on the CeN. These data demonstrate that limbic cortical areas both tune the function of cognitive territories of the striatum and thereby underpin maladaptive cocaine-seeking habits.

          Abstract

          Drug seeking behaviour has habitual neural substrates. Here, Murray et al. show that the basolateral amygdala and central nucleus of the amygdala are necessary to recruit and maintain, respectively, the intrastriatal functional transition that underlies cocaine seeking habits.

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          Most cited references63

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          Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

          Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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            Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum.

            Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which dopamine might integrate information across different cortical/basal ganglia circuits are less well understood. We analyzed a collection of retrograde and anterograde tracing studies to understand how the striatonigrostriatal (SNS) subcircuit directs information flow between ventromedial (limbic), central (associative), and dorsolateral (motor) striatal regions. When viewed as a whole, the ventromedial striatum projects to a wide range of the dopamine cells and receives a relatively small dopamine input. In contrast, the dorsolateral striatum (DLS) receives input from a broad expanse of dopamine cells and has a confined input to the substantia nigra (SN). The central striatum (CS) receives input from and projects to a relatively wide range of the SN. The SNS projection from each striatal region contains three substantia nigra components: a dorsal group of nigrostriatal projecting cells, a central region containing both nigrostriatal projecting cells and its reciprocal striatonigral terminal fields, and a ventral region that receives a specific striatonigral projection but does not contain its reciprocal nigrostriatal projection. Examination of results from multiple tracing experiments simultaneously demonstrates an interface between different striatal regions via the midbrain dopamine cells that forms an ascending spiral between regions. The shell influences the core, the core influences the central striatum, and the central striatum influences the dorsolateral striatum. This anatomical arrangement creates a hierarchy of information flow and provides an anatomical basis for the limbic/cognitive/motor interface via the ventral midbrain.
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              Optogenetic investigation of neural circuits underlying brain disease in animal models.

              Optogenetic tools have provided a new way to establish causal relationships between brain activity and behaviour in health and disease. Although no animal model captures human disease precisely, behaviours that recapitulate disease symptoms may be elicited and modulated by optogenetic methods, including behaviours that are relevant to anxiety, fear, depression, addiction, autism and parkinsonism. The rapid proliferation of optogenetic reagents together with the swift advancement of strategies for implementation has created new opportunities for causal and precise dissection of the circuits underlying brain diseases in animal models.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                14 December 2015
                2015
                : 6
                : 10088
                Affiliations
                [1 ]Department of Psychology, University of Cambridge , Cambridge CB2 3EB, UK
                [2 ]Behavioural and Clinical Neuroscience Institute of the University of Cambridge , Cambridge CB2 1QB, UK
                [3 ]Department of Pharmacology, University of Cambridge , Cambridge CB2 1PD, UK
                [4 ]Groupe de recherche en psychiatrie , Paris GDR3557, France
                [5 ]Laboratoire de Neurosciences Expérimentales et Clinique, INSERM, U1084 , Poitiers F-86022, France
                [6 ]Laboratoire de Neurosciences Expérimentales et Cliniques, Université de Poitiers , Poitiers F-86022, France
                Author notes
                [*]

                These authors contributed equally to this work

                [†]

                These authors jointly supervised this work.

                Author information
                http://orcid.org/0000-0002-8992-7317
                http://orcid.org/0000-0002-7383-372X
                Article
                ncomms10088
                10.1038/ncomms10088
                4682035
                26657320
                3f4abeed-7abc-4ccd-947d-1721b1bcab7d
                Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 10 August 2015
                : 03 November 2015
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