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Btbd11 supports cell-type-specific synaptic function
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DOI：10.1016/j.celrep.2023.112591.png)
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摘要
En 中文
Synapses in the brain exhibit cell-type-specific differences in basal synaptic transmission and plasticity. Here, we evaluated cell-type-specific specializations in the composition of glutamatergic synapses, iden-tifying Btbd11 as an inhibitory interneuron-specific, synapse-enriched protein. Btbd11 is highly conserved across species and binds to core postsynaptic proteins, including Psd-95. Intriguingly, we show that Btbd11 can undergo liquid-liquid phase separation when expressed with Psd-95, support-ing the idea that the glutamatergic postsynaptic density in synapses in inhibitory interneurons exists in a phase-separated state. Knockout of Btbd11 decreased glutamatergic signaling onto parvalbumin-positive interneurons. Further, both in vitro and in vivo, Btbd11 knockout disrupts network activity. At the behavioral level, Btbd11 knockout from interneurons alters exploratory behavior, measures of anxiety, and sensitizes mice to pharmacologically induced hyperactivity following NMDA receptor antagonist challenge. Our findings identify a cell-type-specific mechanism that supports glutamatergic synapse function in inhibitory interneurons-with implications for circuit function and an-imal behavior.
Keyword:
PHASE-SEPARATION
INHIBITORY NEURONS
GAMMA RHYTHM
INTERNEURONS
PLASTICITY
IDENTIFICATION
RECEPTORS
SYNAPSES
STRATEGY
STRESS
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期刊
IF:
6.9
论文数:
1.7W
被引数:
10.2W
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