Hippocampal Interneuronal Dysfunction and Hyperexcitability in Porcine Model of Concussion

Ulyanova, A. V.; Cottone, C.; Adam, C. D.; Maheshwari, N.; Grovola, M. R.; Fruchet, O. E.; Alamar, J.; Koch, P. F.; Johnson, V. E.; Cullen, D. K.; Wolf, J. A.

doi:10.1101/2022.03.08.483543

bioRxiv · 10.1101/2022.03.08.483543

Hippocampal Interneuronal Dysfunction and Hyperexcitability in Porcine Model of Concussion

Ulyanova, A. V.·Cottone, C.·Adam, C. D.·Maheshwari, N.·Grovola, M. R.·Fruchet, O. E.·Alamar, J.·Koch, P. F.·Johnson, V. E.·Cullen, D. K.·Wolf, J. A.

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Abstract

Cognitive impairment is a common symptom following mild traumatic brain injury (mTBI or concussion) and can persist for years in some individuals. Hippocampal slice preparations following closed-head, rotational acceleration injury in swine have previously demonstrated reduced axonal function and hippocampal circuitry disruption. However, electrophysiological changes in hippocampal neurons and their subtypes in a large animal mTBI model have not been examined. Using in vivo electrophysiology techniques, we examined laminar oscillatory field potentials and single unit activity in the hippocampal network 7 days post-injury in anesthetized minipigs. Concussion altered the electrophysiological properties of pyramidal cells and interneurons differently in area CA1. While the firing rate, spike width and amplitude of CA1 interneurons were significantly decreased post-mTBI, these parameters were unchanged in CA1 pyramidal neurons. In addition, CA1 pyramidal neurons in TBI animals were less entrained to hippocampal gamma (40 - 80 Hz) oscillations. Stimulation of the Schaffer collaterals also revealed hyperexcitability across the CA1 lamina post-mTBI. Computational simulations suggest that reported changes in interneuronal physiology may be due to alterations in voltage-gated sodium channels. These data demonstrate that a single concussion can lead to significant neuronal and circuit level changes in the hippocampus, which may contribute to cognitive dysfunction following mTBI.

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Ulyanova, A. V., Cottone, C., Adam, C. D., Maheshwari, N., Grovola, M. R., Fruchet, O. E., Alamar, J., Koch, P. F., Johnson, V. E., Cullen, D. K., Wolf, J. A.. 2022-03-10. Hippocampal Interneuronal Dysfunction and Hyperexcitability in Porcine Model of Concussion. https://doi.org/10.1101/2022.03.08.483543

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