Accelerating and decelerating hippocampal theta oscillations via optogenetic stimulations has opposing effects on spatial working memory

Brain oscillations are a key component of cognitive processing. It is believed that neural oscillations are an indicator of the timing of neuronal activity within and across different brain regions. Theta oscillations (7-9 Hz) are one of many brain rhythmic oscillations involved in information processing. In the rodent hippocampus, theta oscillations are generated by pacemaker GABAergic cells of the medial septal area and combine with local hippocampal computation to support cognitive functions. Previous studies have used optogenetic stimulation to entrain medial septum firing to accelerate hippocampal theta rhythm by 2 Hz or more above the endogenous range to test the role of theta oscillations for cognitive function. These manipulations revealed that the acceleration resulted in memory impairment. However, it is unknown whether the impairment resulted simply from the disruption of an endogenous rhythm, or whether it is specific to these higher frequency stimulations. We used optogenetic techniques to target GABAergic parvalbumin cells in the mouse medial septal area to gain control of the theta rhythm. Using this technique, we entrained the hippocampal theta rhythm to frequencies both above and below the endogenous range. We found that a deceleration of the theta rhythm (to 4 and 6 Hz) did not cause an impairment of the hippocampal-memory task as observed with the accelerated rhythm (to 10 and 12 Hz). Therefore, we show that disruption of an endogenous oscillation does not necessarily result in an impairment of cognitive function. Our study further suggests that a deceleration of theta rhythm could result in an improvement of the hippocampus-dependent memory, and future studies could therefore address whether decelerated theta oscillations in the hippocampus facilitate the functional coupling of the hippocampus with other brain regions