Optogenetic entrainment of the septo-hippocampal circuit is state conditional and attenuates spatial accuracy

Summary The manipulation of pattern generators in order to impose temporal organization on target nodes while accounting for dynamic changes in behavior and cognitive demand remains a significant challenge for the use of neurostimulation as a therapeutic treatment option. While perturbation through optogentic stimulation can reveal circuit mechanisms that create and locally integrate temporal organization, it is unclear whether superseding endogenous signals with artificial oscillations would benefit or impede hippocampus-dependent cognition or how cognitive demand might affect artificial septo-hippocampal entrainment. Optogenetic MS stimulation in wild-type rats in 3 conditions showed that septal input is more likely to supersede endogenous hippocampal LFP oscillations when animals are at rest or performing a hippocampus-dependent spatial accuracy task. Stimulation during a hippocampus-independent task, however, resulted in compensatory endogenous oscillations. Although stimulation effects on the inter-spike interval of hippocampal pyramidal cells mirrored task-conditional theta entrainment of the LFP, place field properties were unaffected. Analyses of spatial behavior indicate that optogenetic stimulation can attenuate performance and specific measures of goal zone estimation accuracy but otherwise does not affect the rat’s ability to navigate to the target quadrant. The results suggest that the behavioral effect of temporally organizing the septo-hippocampal circuit relative to an artificial theta signal is limited to the accuracy of the rat’s approximation of the goal zone location. These results have significant implications for the therapeutic use of optogenetic stimulation as a means of attenuating cognitive deficits associated with temporal discoordination.