Dopamine synchronizes hippocampal-prefrontal networks.

Abstract

Interactions among brain networks support cognition and behavior. Oscillatory activity may contribute by coordinating distant neuronal populations, and identifying mechanisms that dynamically modulate this connectivity is crucial for understanding brain function. Dopamine (DA) is a well-positioned candidate, given its role in altering neuronal excitability and regulating oscillatory cognitive networks connecting the hippocampus (HPC) and prefrontal cortex (PFC). However, how DA modulates HPC-PFC synchrony remains mostly unknown. Here, we recorded HPC and PFC activity in urethane-anesthetized rats while manipulating DA levels. Our results show that DA dose-dependently induces HPC-PFC theta coupling, including non-zero-lag phase synchrony. In PFC single units, DA reduced firing rates while strengthening spike-theta phase locking and shifting the preferred firing phase. Preferential stimulation of D1-like receptors with SKF-38393 or D2-like receptors with quinpirole did not reproduce the complete DA-induced oscillatory pattern, whereas systemic apomorphine, a non-selective DA receptor agonist, produced a distinct dose-dependent modulation of theta phase synchrony. Together, these findings demonstrate that DA rapidly reorganizes HPC-PFC network dynamics, enhancing interareal theta phase coordination and the temporal organization of prefrontal neuronal activity. This network response was not fully reproduced by preferential activation of either D1-like or D2-like receptors alone, pointing to a more complex dopaminergic modulation of HPC-PFC network dynamics.