Lateralization of Hippocampal Dentate Spikes and Sharp-Wave Ripples in Urethane Anesthetized Rats Depends on Cholinergic Tone.

Neural activity and bodily functions are inherently rhythmic and related to each other. The occurrence of hippocampal sharp-wave ripples (SPW-Rs) and dentate spikes (DSs) supporting memory consolidation is regulated by the overall state of the brain, and they also seem to aggregate to a certain phase of the breathing cycle in naturally sleeping mice. Further, SPW-Rs and DSs synchronize to a variable degree between hemispheres, but how this is affected by the neural and bodily state is unclear. Here, we recorded dorsal hippocampal local-field potentials, electrocardiogram, and respiration for several hours under urethane anesthesia in adult male Sprague-Dawley rats. For a subset of rats, we injected atropine (50 mg/kg, i.p.) halfway into the recording to decrease cholinergic and parasympathetic tone. We found variable relation of hippocampal oscillations to breathing phase and none to the cardiac cycle phase. A decrease in breathing rate implying increased parasympathetic tone preceded the start of SPW-R bouts. Roughly 90% of DSs and half of SPW-Rs were unilateral. In most rats, SPW-Rs were more often bilateral during slow breathing compared to faster breathing. Atropine reduced the proportion of bilateral SPW-Rs. Both nonrapid eye movement sleep-like state and atropine increased the proportion of bilateral DSs under urethane anesthesia. Finally, in naturally sleeping rats, both DSs and SPW-Rs were bilateral ~60% of the time. In sum, urethane seems to desynchronize DSs but not SPW-Rs, and a low cholinergic and/or parasympathetic tone seems to dissociate SPW-Rs and to synchronize DSs in the two hippocampi. Whether these findings have relevance in terms of memory consolidation and behavior should be investigated in the future.