Brain Research, 585 (1992) 335-339 © 1992 Elsevier Science Publishers B.V. All rights reserved 0006-8993/92/$05.00 335 BRES 25230 Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat S. Miyazaki ~, Y. Katayama b, B.G. Lyeth a, L.W. Jenkins a, D.S. DeWitt ~, S.J. Goldberg "~, P.G. Newlon a and R.L. Hayes d a From the Division of Neurosurgery, Department of Surgery, Richard Roland Reynolds Neurosurgical Research Laboratories, Medical College of Virginia/ Virginia Commonwealth University, Richmond, VA 23298 (USA), b Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173 (Japan), c Bowman Grey School of Medicine, Department of Anesthesia, Winston-Sak, m, NC (USA) and a Division of Neurosurgery, Unil;ersityof Texas Medical School, Houston, TX (USA) (Accepted 10 March 1992) Key words: Traumatic brain injury; Long-term potentiation; Brain injury; Hippocampus; Rat; CAI This study investigated changes in synaptic responses (population spike and population EPSP) of CAI pyramidal cells of the rat hippocampus to stimulation of the Schaffer collateral/commissural pathways 2-3 h after traumatic brain injury (TBI). TB! was induced by a fluid percussion pulse delivered to the parietal epidural space resulting in loss of righting responses for 4.90-8.98 rain. Prior to tetanic stimulation, changes observed after the injury included: (1) decreases in population spikes threshold but not EPSP thresholds; (2) deceases in maximal amplitude of population spikes as well as EPSPs. TBI also suppressed long-term potentiation (LTP), as evidenced by reductions in post-tetanic increases in population spikes as well as EPSPs. Since LTP may reflect processes involved in memory formation, the observed suppression of LTP may be an electrophysiological correlate of enduring memory deficits previously demonstrated in the same injury model. As with ~evere traumatic brain injury (TBI) ~7, even mild-to.moderate levels of TBI in humans are com- monly associated with persistent disturbances in mem- ory (e.g. refs. 3, 10, 16, 28, 29, 30). In humans sustain- ing mild.to-moderate TBI anatomical correlates of memory deficits are unknown because the low inci- dence of mortality precludes histological examination. Experimental studies in rats have shown that moderate TBI produces deficits in short-term spatial memory which can persist for 15 days ~9'2°'27. Lesions of the rodent amygdala and/or hippocampus produced by cerebral ischemia results in spatial memory deficits 25'35 even when restricted to loss of hippocampal CA1 neu- rons 2'33. However, since spatial memory deficits after TBI occur in the absence of hippocampal neuronal death ~9'2° or ultrastructural changes 22 enduring sub- lethal functional changes in hippocampal neurons may underlie these deficits. This research attempted to examine these enduring sublethal changes in neuronal function mediating memory deficits after TBI. We examined the effects of TBI on long-term potentiation (LTP) which is thought to be an eleetroph~iological correlate of memory func- tion 3~. LTP was studied in CA1 cells of the hippocam- pus because of substantial data indicating that induc- tion of LTP in these neurons may play a crucial role in encoding memo~; 2'4'~'2t'33 and are preferentially vul- nerable to secondary insults following TBI tz~3. in the first such study, we report here that TBI suppresses LTP of CAI neurons when examined at 2-3 h after TBI. Seventeen male Sprague-Dawley rats (280-345 g) were used. The TBI, described in detail elsewhere s' ~t,~4,~s was administered by delivering a pressure tran- sient produced by a fluid pulse within the epidural space. Rats were surgically prepared under sodium Correspondence: R.L. Hayes, Division of Neurosurgery, University of Texas Medical School at Houston, 5431 Fannin, Suite 7.148, Houston, TX 77030, USA. Fax: (1) (713) 794-5084.