Cell-autonomous GABAARs are essential for NMDAR-mediated synaptic transmission, LTP, and spatial memory

ABSTRACT: 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

SUBMITTER: Jing, jing duan 

PROVIDER: S-SCDT-10_1038-S44319-025-00538-X | biostudies-other |

REPOSITORIES: biostudies-other