SHANK3 controls maturation of social reward circuits in the VTA.
Nat Neurosci. 2016-06-06; 19(7): 926-934
DOI: 10.1038/nn.4319
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1. Nat Neurosci. 2016 Jul;19(7):926-934. doi: 10.1038/nn.4319. Epub 2016 Jun 6.
SHANK3 controls maturation of social reward circuits in the VTA.
Bariselli S(#)(1), Tzanoulinou S(#)(1), Glangetas C(1)(2)(3), Prévost-Solié C(1),
Pucci L(1), Viguié J(4), Bezzi P(1), O’Connor EC(4), Georges F(2)(3)(5), Lüscher
C(4)(6), Bellone C(1).
Author information:
(1)Dept. of Fundamental Neurosciences, University of Lausanne, CH-1005, Lausanne,
Switzerland.
(2)Centre National de la Recherche Scientifique, Interdisciplinary Institute for
Neuroscience, UMR 5297, Bordeaux, France.
(3)Université de Bordeaux, Bordeaux, France.
(4)Dept. of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211
Geneva, Switzerland.
(5)Centre National de la Recherche Scientifique, Neurodegeneratives diseases
Institute, UMR 5293, Bordeaux, France.
(6)Clinic of Neurology, Geneva University Hospital, CH-1211 Geneva, Switzerland.
(#)Contributed equally
Comment in
Nat Neurosci. 2016 Jun 28;19(7):864-6.
Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3,
leads to a highly penetrant form of autism spectrum disorder. How SHANK3
insufficiency affects specific neural circuits and how this is related to
specific symptoms remains elusive. Here we used shRNA to model Shank3
insufficiency in the ventral tegmental area of mice. We identified dopamine (DA)
and GABA cell-type-specific changes in excitatory synapse transmission that
converge to reduce DA neuron activity and generate behavioral deficits, including
impaired social preference. Administration of a positive allosteric modulator of
the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal
week restored DA neuron excitatory synapse transmission and partially rescued the
social preference defects, while optogenetic DA neuron stimulation was sufficient
to enhance social preference. Collectively, these data reveal the contribution of
impaired ventral tegmental area function to social behaviors and identify mGluR1
modulation during postnatal development as a potential treatment strategy.
DOI: 10.1038/nn.4319
PMCID: PMC4948673
PMID: 27273769 [Indexed for MEDLINE]