Independently tunable subcortical oscillators enable prefrontal control of cortical coupling
- 1University of Lausanne
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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BibTeX
@misc{mozaffarilegha2026independently,
title = {{Independently tunable subcortical oscillators enable prefrontal control of cortical coupling}},
author = {M. Mozaffarilegha and A. Kolaxi and V. Nikoletopoulou and H. T. Ito},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758762},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758762v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Independently tunable subcortical oscillators enable prefrontal control of cortical coupling
AU - M. Mozaffarilegha
AU - A. Kolaxi
AU - V. Nikoletopoulou
AU - H. T. Ito
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758762
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758762v1
AB - 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.
ER -