Abstract
Understanding how neuronal circuits stabilize their activity is a fundamental yet poorly understood aspect of neuroscience. Here, we show that hippocampal network properties, such as firing rate distribution and dimensionality, are actively regulated, despite perturbations and single-cell drift. 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. This establishes a new network firing rate set point via NMDAR-eEF2K signaling pathway. NMDARs’ capacity to modulate and stabilize network firing is mediated by excitatory synapses and the intrinsic excitability of parvalbumin-positive neurons, respectively. In behaving mice, continuous NMDAR blockade in CA1 reduces network firing without altering single-neuron drift or triggering a compensatory response. These findings expand NMDAR function beyond their canonical role in synaptic plasticity and raise the possibility that some NMDAR-dependent behavioral effects are mediated by their unique regulation of population activity set points.
Original language | English |
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Pages (from-to) | 244-259.e7 |
Journal | Neuron |
Volume | 113 |
Issue number | 2 |
Early online date | 5 Nov 2024 |
DOIs | |
State | Published - 22 Jan 2025 |
Keywords
- BDNF
- CA1 hippocampus
- NMDA receptors
- PV interneurons
- drift
- eEF2K
- firing rate homeostasis
- ketamine
- set point
All Science Journal Classification (ASJC) codes
- General Neuroscience