21
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Drd3 Signaling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Early life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood. Using in vivo Ca 2+ imaging, we found that Drd3-expressing-LS (Drd3 LS) neurons in animals exposed to ELS show blunted activity in response to social stimuli. In addition, optogenetic activation of Drd3 LS neurons rescues ELS-induced social impairments. Furthermore, pharmacological treatment with a Drd3 agonist, which increases Drd3 LS neuronal activity, normalizes the social dysfunctions of ELS mice. Thus, we identify Drd3 in the LS as a critical mediator and potential therapeutic target for the social abnormalities caused by ELS.

          Highlights

          • Early social deprivation (ESD) causes downregulation of Drd3 signaling in the LS

          • Blunted LS Drd3 neuronal activity mediate ESD-induced social dysfunctions

          • Drd3 signaling has corresponding effects on neuronal activity in the LS

          • Activation of Drd3 signaling in the LS normalize social impairments of ESD mice

          Abstract

          Exposure to early adverse experiences is associated with an increased risk of developing social dysfunction later in life. Shin et al. show that Drd3 signaling and its corresponding effects on neural activity in the LS are both necessary and sufficient to cause early life stress-induced social abnormalities in adulthood.

          Related collections

          Most cited references62

          • Record: found
          • Abstract: found
          • Article: not found

          Behavioural phenotyping assays for mouse models of autism.

          Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100-150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of autism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mechanisms in the cycle of violence.

              Two questions concerning the effect of physical abuse in early childhood on the child's development of aggressive behavior are the focus of this article. The first is whether abuse per se has deleterious effects. In earlier studies, in which samples were nonrepresentative and family ecological factors (such as poverty, marital violence, and family instability) and child biological variables (such as early health problems and temperament) were ignored, findings have been ambiguous. Results from a prospective study of a representative sample of 309 children indicated that physical abuse is indeed a risk factor for later aggressive behavior even when the other ecological and biological factors are known. The second question concerns the processes by which antisocial development occurs in abused children. Abused children tended to acquire deviant patterns of processing social information, and these may mediate the development of aggressive behavior.
                Bookmark

                Author and article information

                Contributors
                Journal
                Neuron
                Neuron
                Neuron
                Cell Press
                0896-6273
                1097-4199
                03 January 2018
                03 January 2018
                : 97
                : 1
                : 195-208.e6
                Affiliations
                [1 ]Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
                [2 ]Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
                [3 ]Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
                Author notes
                []Corresponding author bklim@ 123456ucsd.edu
                [4]

                Lead Contact

                Article
                S0896-6273(17)31121-2
                10.1016/j.neuron.2017.11.040
                5766830
                29276054
                a39ece59-d6ac-4ed1-a879-31c2460225ac
                © 2017 Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 6 June 2017
                : 17 October 2017
                : 29 November 2017
                Categories
                Article

                Neurosciences
                early life stress,early social deprivation,lateral septum,drd3,social dysfunction,pd128907

                Comments

                Comment on this article