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Btbd11 regulates glutamatergic synapse organization in GABAergic inhibitory interneurons.

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Btbd11 supports cell-type-specific synaptic function.

Alexei M Bygrave1, Ayesha Sengupta2, Ella P Jackert1

  • 1Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Cell Reports
|June 1, 2023
PubMed
Summary
This summary is machine-generated.

Researchers identified Btbd11, a protein crucial for glutamatergic synapses in inhibitory interneurons. Its absence disrupts brain network activity and alters animal behavior, highlighting its role in neuronal function.

Keywords:
Btbd11CP: Neurosciencebehaviorglutamatergic synapseinhibitory interneuronsliquid-liquid phase separationneuronal circuitparvalbuminproteomics

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Synaptic transmission and plasticity vary across brain cell types.
  • Understanding cell-type-specific synaptic composition is key to deciphering circuit function.

Purpose of the Study:

  • To investigate cell-type-specific specializations in glutamatergic synapse composition.
  • To identify novel proteins involved in inhibitory interneuron function.

Main Methods:

  • Identified Btbd11 as an inhibitory interneuron-specific protein enriched at synapses.
  • Investigated Btbd11's interaction with postsynaptic density protein 95 (Psd-95) and its role in liquid-liquid phase separation.
  • Utilized knockout models (in vitro and in vivo) to assess the impact of Btbd11 deletion on glutamatergic signaling, network activity, and behavior.

Main Results:

  • Btbd11 is a conserved, synapse-enriched protein specific to inhibitory interneurons.
  • Btbd11 interacts with Psd-95 and can undergo liquid-liquid phase separation, suggesting phase-separated postsynaptic densities in these neurons.
  • Btbd11 knockout reduced glutamatergic signaling onto parvalbumin-positive interneurons, disrupted network activity, and altered exploratory behavior and anxiety levels in mice.

Conclusions:

  • Btbd11 is a critical regulator of glutamatergic synapse function in inhibitory interneurons.
  • Btbd11 plays a significant role in maintaining brain circuit homeostasis and normal animal behavior.
  • These findings reveal a cell-type-specific mechanism with implications for understanding neurological disorders.