Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Apr 30

PMID 31031006

Citations 153

Authors

Jun Nagai

Abha K Rajbhandari

Mohitkumar R Gangwani

Ayaka Hachisuka

Giovanni Coppola

Sotiris C Masmanidis

Michael S Fanselow

Baljit S Khakh

Affiliations

Soon will be listed here.

Abstract

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 (GABA) 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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