Oxytocin selectively biases sensory-prefrontal communication in mice by suppressing baseline activity and enhancing theta coupling

Understanding how local neuromodulation translates to selective processing across distributed brain systems is crucial for comprehending complex behaviors like social information processing. While oxytocin is known to alter excitatory-inhibitory balance at the microcircuit level, its impact on large-scale neurodynamics within the cortico-limbic network remains unclear. Current models often struggle to explain how a global neuromodulator can achieve selective enhancement of specific sensory inputs without broadly increasing excitability, highlighting a significant gap in our understanding of oxytocin's systems-level effects.

Researchers investigated oxytocin's effects on large-scale neurodynamics in the mouse brain using multisite local field potential (LFP) recordings. Mice were administered oxytocin or saline, and neural activity was monitored during responses to infant calls, auditory steady-state responses (ASSRs), and rest. The study focused on the auditory cortex (AC) and medial prefrontal cortex (mPFC). Primary endpoints included neural response amplitude, baseline activity, prefrontal phase coherence, spontaneous spectral power, and interregional phase coupling and directional connectivity between AC and mPFC.

Oxytocin selectively enhanced neural responses to infant calls in both the auditory cortex (AC) and medial prefrontal cortex (mPFC). These enhancements occurred concurrently with a reduction in baseline activity, indicating an increased signal-to-noise ratio rather than a global excitability boost. During ASSRs, oxytocin increased prefrontal phase coherence without altering ASSR power. At rest, oxytocin induced a transient, broadband reduction in spontaneous spectral power across regions. Despite this overall reduction, analyses of interregional interactions revealed a selective increase in low-theta phase coupling and directional connectivity from AC→mPFC. Session-level analyses showed that stronger bottom-up AC→mPFC coupling was associated with lower prefrontal power.

This finding is consistent with a gating or disinhibitory network regime that favors sensory-to-prefrontal information transfer. Multivariate analyses demonstrated that oxytocin/saline conditions were reliably discriminable using supervised classification models, with specific contributions from spectral power, phase-locking, and Granger-causal connectivity features.