Rhythmic oscillations within the 3-12 Hz theta frequency band manifest in the rodent hippocampus during a variety of behaviors and are particularly well characterized during spatial navigation. In contrast, previous studies of rhythmic hippocampal activity in primates under comparable behavioral conditions suggest it may be less apparent and possibly less prevalent, or even absent, compared to the rodent. We compared the relative presence of low frequency oscillations in rats and humans during spatial navigation by employing an oscillation detection algorithm (“P-episode” or “BOSC”) to better characterize their presence in microelectrode local field potential (LFP) recordings. This method quantifies the proportion of time the LFP exceeds both a power and cycle duration threshold at each frequency, characterizing the presence of 1) oscillatory activity compared to background noise, 2) the peak frequency of oscillatory activity, and 3) the duration of oscillatory activity. Results demonstrate that both humans and rodents have hippocampal rhythmic fluctuations lasting, on average, 2.75 and 4.3 cycles, respectively. Analyses further suggest that human hippocampal rhythmicity is centered around ~3Hz while that of rats is centered around ~8Hz. These results establish that low frequency rhythms relevant to spatial navigation are present in both the rodent and human hippocampus, albeit with different properties under the behavioral conditions tested.

More than 5,000,000 survivors of traumatic brain injury (TBI) live with persistent cognitive deficits, some of which likely derive from hippocampal dysfunction. Oscillatory activity in the hippocampus is critical for normal learning and memory functions, and can be modulated using deep brain stimulation techniques. In this pre-clinical study, we demonstrate that lateral fluid percussion TBI results in the attenuation of hippocampal theta oscillations in the first 6 days after injury, which correlate with deficits in the Barnes maze spatial working memory task. Theta band stimulation of the medial septal nucleus (MSN) results in a transient increase in hippocampal theta activity, and when delivered 1 min prior to training in the Barnes maze, it significantly improves spatial working memory. These results suggest that MSN theta stimulation may be an effective neuromodulatory technique for treatment of persistent learning and memory deficits after TBI.

Traumatic brain injury (TBI) often results in persistent attention and memory deficits that are associated with hippocampal dysfunction. Although deep brain stimulation (DBS) is used to treat neurological disorders related to motor dysfunction, the effectiveness of stimulation to treat cognition remains largely unknown. In this study, adult male Harlan Sprague-Dawley rats underwent a lateral fluid percussion or sham injury followed by implantation of bipolar electrodes in the medial septal nucleus (MSN) and ipsilateral hippocampus. In the first week after injury, there was a significant decrease in hippocampal theta oscillations that correlated with decreased object exploration and impaired performance in the Barnes maze spatial learning task. Continuous 7.7 Hz theta stimulation of the medial septum significantly increased hippocampal theta oscillations, restored normal object exploration, and improved spatial learning in injured animals. There were no benefits with 100 Hz gamma stimulation, and stimulation of sham animals at either frequency did not enhance performance. We conclude, therefore, that there was a theta frequency-specific benefit of DBS that restored cognitive function in brain-injured rats. These data suggest that septal theta stimulation may be an effective and novel neuromodulatory therapy for treatment of persistent cognitive deficits following TBI.