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Fast Spiking Interneurons Autonomously Generate Fast Gamma Oscillations in the Medial Entorhinal Cortex with
Brandon Williams1, Ananth Vedururu Srinivas2, Roman Baravalle2
1Department of Biomedical Engineering, Center for Systems Neuroscience, Neurophotonics Center, Boston University, Boston, Massachusetts 02215.
Eneuro
|January 20, 2026
Summary
Fast-spiking interneurons in the medial entorhinal cortex can autonomously generate gamma rhythms via interneuron network gamma (ING). Excitatory drive strength tunes oscillations between fast ING and slower pyramidal-interneuron network gamma (PING) regimes.
Area of Science:
- Neuroscience
- Computational Neuroscience
- Systems Neuroscience
Background:
- Gamma oscillations (40-140 Hz) in the medial entorhinal cortex (mEC) are crucial for cognitive functions like spatial navigation and memory.
- Existing models propose pyramidal-interneuron network gamma (PING) and interneuron network gamma (ING) mechanisms, but the role of inhibitory circuits is not fully understood.
Purpose of the Study:
- To investigate the precise role of inhibitory circuits in generating gamma oscillations within the mEC.
- To determine how excitatory and inhibitory interactions influence the oscillatory regime (frequency and mechanism) in the mEC.
Main Methods:
- Utilized optogenetic stimulation and whole-cell electrophysiology in acute mouse brain slices to examine synaptic input and neuronal firing.
- Investigated the contribution of AMPA/kainate receptors and selectively activated PV+ interneurons.
- Developed computational network models constrained by experimental data to simulate network dynamics.
Main Results:
- Fast-spiking interneurons exhibited robust gamma firing, while excitatory neurons showed gamma cycle skipping.
- Gamma activity persisted after AMPA/kainate receptor blockade, indicating a functional ING mechanism.
- Computational models showed that weak excitatory input favors fast ING rhythms, while stronger input shifts to slower PING rhythms.
Conclusions:
- Inhibitory circuits, particularly fast-spiking interneurons, play a dominant role in sustaining gamma rhythms in the mEC.
- The strength of excitatory drive dynamically tunes the oscillatory regime, influencing the balance between ING and PING mechanisms.
- Findings refine models of entorhinal gamma oscillations, suggesting a hybrid mechanism critical for spatial computation.
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