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      Effects of mGlu4 knock-down in the nucleus accumbens and basolateral amygdala of wild-type mice

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          Abstract

          Autism Spectrum Disorders (ASD) are neuro-developmental pathologies characterized by social communication and interaction deficiency, and repetitive and restricted behaviors. The social motivation network, notably the nucleus accumbens (NAc), is dysfunctional in these disorders. We previously showed that pharmacological treatment facilitating the activity of the mGlu4 glutamate receptor relieves autistic symptoms in the Oprm1 -/- mouse model of autism. Interestingly, we also evidenced that mGlu4 can modulate the activity of the amygdala, a critical brain region for emotional responses and social behavior.

          Aim: Our hypothesis is mGlu4 in the NAc and the basolateral amygdala (BLA) plays a critical role in modulating autism-sensitive symptoms, namely social motivation and stereotyped behaviors.

          Methods : In order to test this, we performed the knockdown of the gene coding for mGlu4, Grm4, in the nucleus accumbens or the basolateral amygdala of wild-type mice using bilateral stereotaxic injections of shRNA-expressing AAVs. We tested them in several behavioral tests to evaluate the presence or not of autistic symptoms.

          Results: Knocking down (KD) of Grm4 expression in NAc neurons induces autistic-like symptoms such as impaired social interactions and social preference

          Conclusions : These results suggest that mGlu4 receptors expressed in the NAc and BLA neurons play a major role in modulating sociability in mice.

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          Author and article information

          Journal
          ScienceOpen Posters
          ScienceOpen
          1 July 2020
          Affiliations
          [1 ] UMR Inserm U 1253 - Imagerie et Cerveau (iBrain), Tours, France
          [2 ] Hertie Institute for Clinical Brain Research & Centre for Integrative Neuroscience Otfried-Müller Str. 25D-72076 ; Tübingen, Germany
          [3 ] University of Stuttgart
          [4 ] Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, Inserm U1258, Université de Strasbourg
          [5 ] Inserm U 1253 - Imagerie et Cerveau (iBrain), Tours, France
          [6 ] CNRS UMR7247, Inserm U 1253 - Imagerie et Cerveau (iBrain), Tours, France
          Article
          10.14293/S2199-1006.1.SOR-.PP4OHCX.v1

          This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

          The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

          Life sciences

          BLA, Autism, mGlu4, NAc

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