Disruption of footshock-induced theta rhythms by stimulating median raphe nucleus reduces anxiety in rats

• Inescapable footshock stimulation increases LF theta rhythms and anxiety.
• High frequency (100 Hz) stimulation of MRN desynchronizes LF theta power.
• Administration of bicuculline into MRN decreases LF theta power.
• Desynchronization of LF oscillations reduces footshock-induced anxiety.

Theta rhythms generated in the hippocampus are controlled by the pacemaker in the medial septum-diagonal band of Broca (MS-DBB). The median raphe nucleus (MRN) transmits serotonergic signals to the MS-DBB, which suppresses the septo-hippocampus-produced theta waves, whereas GABAergic interneurons in the MRN facilitate the generation of theta oscillations. Animal studies have indicated that fear increases theta oscillations. Moreover, anxiolytics reduce reticular formation-elicited theta rhythms and theta blockade decreases anxiety. In this study, we hypothesized that the MRN mediates anxiety reduction caused by the theta blockade. Our results demonstrated that inescapable-footshock stimulation significantly increased the power of low-frequency theta oscillations (4–7 Hz) in rats. Both the electrical stimulation of MRN and administration of bicuculline into the MRN successfully desynchronized footshock-induced theta oscillations. Compared to the naïve rats, inescapable-footshock stimulation diminished the entry percentage and time spent in the open arms of the elevated plus maze (EPM), behavioral indicators of anxiety. Rats treated with either MRN stimulation or bicuculline administration to desynchronize theta oscillations reduced anxiety caused by the inescapable-footshock stimulation. Our results demonstrated that the electrical stimulation of MRN or blockade of the GABAergic pathways in the MRN interferes with theta oscillations and reduces anxiety, implicating the role of MRN.