NORADRENERGIC MODULATION OF HIPPOCAMPAL-PREFRONTAL DYNAMICS DURING REWARD-GUIDED NAVIGATION

Learning requires the brain to flexibly transition between internal modes supporting exploration, online processing, and memory consolidation. Noradrenaline (NE), released primarily by locus coeruleus projections, is a key regulator of global brain state, yet how moment-to-moment fluctuations in NE shape hippocampal–prefrontal communication during learning remains poorly understood.
Here, we combine genetically encoded NE sensors with simultaneous high-density Neuropixels recordings in dorsal hippocampus (HPC) and medial prefrontal cortex (mPFC) to examine how neuromodulatory state reorganizes large-scale circuit dynamics during spatial learning. Head-fixed mice perform a treadmill-based task in which reward location is systematically shifted across sessions, eliciting prediction errors and updating spatial representations.
Continuous GRAB-NE photometry provides a temporally resolved measure of noradrenergic state, while Neuropixels recordings capture single-neuron activity, local field potentials, and cross-regional population structure. We investigate how fluctuations in NE relate to changes in hippocampal–prefrontal coupling, population synchrony, and memory-related events such as sharp-wave ripples.
Specifically, we test whether distinct neuromodulatory states bias the circuit toward an alert, encoding-dominated mode characterized by enhanced theta-band coupling, versus a consolidation-favoring mode associated with ripple-mediated reactivation and cross-regional assembly coordination. By linking noradrenergic dynamics to interareal communication and learning behavior, this work aims to reveal how neuromodulatory state governs the balance between encoding new information and consolidating past experience.