دورية
Schizophrenia-associated LRRTM1 regulates cognitive behavior through controlling synaptic function in the mediodorsal thalamus
| العنوان: | Schizophrenia-associated LRRTM1 regulates cognitive behavior through controlling synaptic function in the mediodorsal thalamus |
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| المؤلفون: | Karimi, Benyamin, Silwal, Prabhisha, Booth, Samuel, Padmanabhan, Nirmala, Dhume, Shreya H., Zhang, Dali, Zahra, Nazmeena, Jackson, Michael F., Kirouac, Gilbert J., Ko, Ji Hyun, Chopek, Jeremy W., Siddiqui, Tabrez J. |
| المصدر: | Molecular Psychiatry; 20210101, Issue: Preprints p1-14, 14p |
| مستخلص: | Reduced activity of the mediodorsal thalamus (MD) and abnormal functional connectivity of the MD with the prefrontal cortex (PFC) cause cognitive deficits in schizophrenia. However, the molecular basis of MD hypofunction in schizophrenia is not known. Here, we identified leucine-rich-repeat transmembrane neuronal protein 1 (LRRTM1), a postsynaptic cell-adhesion molecule, as a key regulator of excitatory synaptic function and excitation-inhibition balance in the MD. LRRTM1is strongly associated with schizophrenia and is highly expressed in the thalamus. Conditional deletion of Lrrtm1in the MD in adult mice reduced excitatory synaptic function and caused a parallel reduction in the afferent synaptic activity of the PFC, which was reversed by the reintroduction of LRRTM1 in the MD. Our results indicate that chronic reduction of synaptic strength in the MD by targeted deletion of Lrrtm1functionally disengages the MD from the PFC and may account for cognitive, social, and sensorimotor gating deficits, reminiscent of schizophrenia. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 13594184 14765578 |
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| DOI: | 10.1038/s41380-021-01146-6 |