NMDA receptors regulate the firing rate set point of hippocampal circuits
NMDARs are central regulators of Hebbian synaptic plasticity, although their role in neuronal homeostasis is debated.
The researchers in this study reveal a novel role for NMDARs in regulating network, but not single-neuron, firing rate set points to which compensatory mechanisms are tuned. Continuous inhibition of N-methyl-D-aspartate receptors (NMDARs) ex vivo lowers the excitation/inhibition ratio and network firing rates while preserving resilience to perturbations.
PV-interneuronintrinsic plasticity, through eEF2K signaling, stabilizes the new set point, offering insights into NMDARs’ therapeutic potential. Continuous NMDAR blockade in CA1 in mice, reduces network firing without altering single-neuron drift or triggering a compensatory response.
