Jing-Jing Duan, Bin Jiang, Wei Yin, Yuan Lin, Guang-Mei Yan, Wei Lu
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Cell-autonomous GABAARs are essential for NMDAR-mediated synaptic transmission, LTP, and spatial memory.
GABAA receptors (GABAARs) mediate most synaptic inhibition in the brain, but their cell-autonomous role in regulating glutamatergic transmission remains poorly understood. By targeting GABAAR β1-3 subunit alleles (GABRB1-3) at once, we genetically eliminated GABAARs in individual hippocampal CA1 pyramidal neurons. We find that single-cell silencing of GABAergic transmission does not alter AMPAR-mediated synaptic transmission, but leads to a reduction in NMDAR-mediated synaptic transmission, loss of long-term potentiation (LTP), and impaired spatial memory. Genetic rescue experiments reveal that NMDAR-mediated whole-cell currents and synaptic transmission depend on specific GABAAR subtypes and are tightly regulated by neuronal excitability. Pharmacologically restoring NMDAR function in β123-CRISPR mice rescues both LTP and spatial memory deficits induced by the loss of GABAARs in CA1 neurons. Our data uncover a previously unknown regulation of synaptic NMDAR functions by GABAARs at the single-cell level and provide insight into excitation and inhibition balance between GABAARs and NMDARs in the brain.
期刊介绍：
EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings.
The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that:
Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels.
Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies.
Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding.
Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts.
EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.
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