Prefrontal-hippocampal coupling by theta rhythm and by 2–5 Hz oscillation in the delta band: The role of the nucleus reuniens of the thalamus

Rhythmic synchronizations of hippocampus (HC) and prefrontal cortex (PFC) at theta frequencies (4–8 Hz) are thought to mediate key cognitive functions, and disruptions of HC-PFC coupling were implicated in psychiatric diseases. Theta coupling is thought to represent a HC-to-PFC drive transmitted via the well-described unidirectional HC projection to PFC. In comparison, communication in the PFC-to-HC direction is less understood, partly because no known direct anatomical connection exists. Two recent findings, i.e., reciprocal projections between the thalamic nucleus reuniens (nRE) with both PFC and HC and a unique 2–5 Hz rhythm reported in the PFC, indicate, however, that a second low-frequency oscillation may provide a synchronizing signal from PFC to HC via nRE. Thus, in this study, we recorded local field potentials in the PFC, HC, and nRE to investigate the role of nRE in PFC–HC coupling established by the two low-frequency oscillations. Using urethane-anesthetized rats and stimulation of pontine reticular formation to experimentally control the parameters of both forebrain rhythms, we found that theta and 2–5 Hz rhythm were dominant in HC and PFC, respectively, but were present and correlated in all three signals. Removal of nRE influence, either statistically (by partialization of PFC–HC correlation when controlling for the nRE signal) or pharmacologically (by lidocaine microinjection in nRE), resulted in decreased coherence between the PFC and HC 2–5-Hz oscillations, but had minimal effect on theta coupling. This study proposes a novel thalamo-cortical network by which PFC-to-HC coupling occurs via a 2–5 Hz oscillation and is mediated through the nRe.