A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling

Area of Science:

• Neuroscience
• Cellular signaling

Background:

• ErbB4 receptor is key in GABAergic interneurons and neural synchronization.
• Endogenous ligands, activation processes, and targets of ErbB4 signaling remain largely unknown.

Purpose of the Study:

• Investigate the role of NMDA receptors in neuregulin/ErbB4 signaling within cortical interneurons.
• Elucidate the downstream effects of this signaling pathway on neuronal function.

Main Methods:

• Utilized cultured neurons and acute brain slices for experimental analysis.
• Examined the interaction between NMDA receptors, ErbB4, and neuregulin 2 (NRG2).

Main Results:

• NMDA receptor activation triggers shedding of NRG2's extracellular domain.
• NRG2 binding leads to ErbB4 association with GluN2B-containing NMDA receptors.
• This interaction causes rapid internalization of NMDA receptors, downregulating NMDA currents selectively in ErbB4-positive interneurons.

Conclusions:

• Established a reciprocal relationship between ErbB4 and NMDA receptors in cortical interneurons.
• Findings suggest implications for understanding cortical microcircuit modulation in psychiatric disorders.