Abstract
INTRODUCTION: Traumatic brain injury (TBI) can lead to profound deficits of learning and memory that can be a source of considerable morbidity. We investigated hippocampal firing patterns after TBI and the effect of hippocampal theta burst stimulation (TBS) on bursting and cognitive recovery after TBI. METHODS: Twenty-four male Sprague-Dawley rats were used in the study; twelve underwent mild fluid percussion injury (FPI, 1.5 Atm) and were compared to twelve sham-operated rats. Twelve rats (6 TBI, 6 sham) underwent bilateral implantation of electrodes into the CA1 and CA3 hippocampal subfields, and twelve rats (6 TBI, 6 sham) underwent implantation of a stimulating electrode into the fornix. Rats were trained to perform in a delayed nonmatch-to-place swim T-maze. Single neuron busting activity and maze performance were analyzed during task performance 30-90 days after trauma. Theta burst stimulation (TBS, 200 Hz in 50 ms trains, 5 trains per second, 60 μA biphasic pulses) was delivered to the fornix electrodes during task performance in implanted animals. RESULTS: There were no histological differences between control and mTBI rats, and stereological analysis demonstrated no neuronal loss. Rats subjected to mTBI demonstrated significantly poorer performance on the memory task compared with sham rats. Examination of single-neuron spiking activity during exploratory activity revealed that TBI was associated with significantly less hippocampal bursting (P < .05) with a trend toward longer bursts and lower inter-burst spike frequency in the TBI group. Burst stimulation of the fornix normalized cognitive performance in the TBI group to levels indistinguishable from the sham group. CONCLUSION: Deficits in learning and memory after TBI are associated with decreased hippocampal burst activity and are improved with TBS of the hippocampus.
Published Version
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