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Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue.
Nagai, Jun; Rajbhandari, Abha K; Gangwani, Mohitkumar R; Hachisuka, Ayaka; Coppola, Giovanni; Masmanidis, Sotiris C; Fanselow, Michael S; Khakh, Baljit S.
Afiliação
  • Nagai J; Department of Physiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Rajbhandari AK; Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Gangwani MR; Department of Physiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Hachisuka A; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Coppola G; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Huma
  • Masmanidis SC; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Fanselow MS; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Khakh BS; Department of Physiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA. Electronic address: bkhakh@mednet.ucla.edu.
Cell ; 177(5): 1280-1292.e20, 2019 05 16.
Article em En | MEDLINE | ID: mdl-31031006
Hyperactivity and disturbances of attention are common behavioral disorders whose underlying cellular and neural circuit causes are not understood. We report the discovery that striatal astrocytes drive such phenotypes through a hitherto unknown synaptic mechanism. We found that striatal medium spiny neurons (MSNs) triggered astrocyte signaling via γ-aminobutyric acid B (GABAB) receptors. Selective chemogenetic activation of this pathway in striatal astrocytes in vivo resulted in acute behavioral hyperactivity and disrupted attention. Such responses also resulted in upregulation of the synaptogenic cue thrombospondin-1 (TSP1) in astrocytes, increased excitatory synapses, enhanced corticostriatal synaptic transmission, and increased MSN action potential firing in vivo. All of these changes were reversed by blocking TSP1 effects. Our data identify a form of bidirectional neuron-astrocyte communication and demonstrate that acute reactivation of a single latent astrocyte synaptogenic cue alters striatal circuits controlling behavior, revealing astrocytes and the TSP1 pathway as therapeutic targets in hyperactivity, attention deficit, and related psychiatric disorders.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Sinapses / Comportamento Animal / Transdução de Sinais / Comunicação Celular / Astrócitos / Neurônios Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Sinapses / Comportamento Animal / Transdução de Sinais / Comunicação Celular / Astrócitos / Neurônios Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos