Independently tunable subcortical oscillators enable prefrontal control of cortical coupling

Authors

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

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 15 Oct 2026.

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