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bioRxiv · 10.64898/2026.10.13.758762

Independently tunable subcortical oscillators enable prefrontal control of cortical coupling

Mozaffarilegha, M.·Kolaxi, A.·Nikoletopoulou, V.·Ito, H. T.
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Abstract

Oscillatory coherence between brain regions varies flexibly with behavioral demands, yet the circuit mechanism underlying this control remains unclear. Theta rhythm, which coordinates prefrontal-hippocampal activity, is classically attributed to a pacemaker in the medial septum (MS), with the supramammillary nucleus (SuM) as its modulator. Here we show that SuM instead operates as an independently tunable theta oscillator. In rats performing a spatial alternation task, SuM theta frequency decreased before the choice point while MS theta frequency remained stable, reducing the SuM-MS frequency mismatch in both population spiking and local field potentials. The size of this mismatch predicted theta-rhythm coordination between the medial prefrontal cortex (mPFC) and hippocampal CA1 in both the alternation task and open-field foraging. Inhibiting direct mPFC input to SuM abolished the behavior-dependent modulation of SuM frequency and disrupted mPFC-CA1 coupling. These findings place a subcortical theta oscillator under top-down prefrontal control and identify the SuM-MS frequency mismatch as a control variable for interregional coordination.

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Mozaffarilegha, M., Kolaxi, A., Nikoletopoulou, V., Ito, H. T.. 2026-10-14. Independently tunable subcortical oscillators enable prefrontal control of cortical coupling. https://doi.org/10.64898/2026.10.13.758762

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