| First Author | Nagai J | Year | 2019 |
| Journal | Cell | Volume | 177 |
| Issue | 5 | Pages | 1280-1292.e20 |
| PubMed ID | 31031006 | Mgi Jnum | J:285369 |
| Mgi Id | MGI:6389861 | Doi | 10.1016/j.cell.2019.03.019 |
| Citation | Nagai J, et al. (2019) Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue. Cell 177(5):1280-1292.e20 |
| abstractText | 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 gamma-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. |
