Rapid changes in synaptic strength after mild traumatic brain injury

Ellen D. Witkowski, Yuan Gao, Alexander F. Gavsyuk, Ido Maor, Gloria J. DeWalt, William D. Eldred, Adi Mizrahi, Ian G. Davison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Traumatic brain injury (TBI) affects millions of Americans annually, but effective treatments remain inadequate due to our poor understanding of how injury impacts neural function. Data are particularly limited for mild, closed-skull TBI, which forms the majority of human cases, and for acute injury phases, when trauma effects and compensatory responses appear highly dynamic. Here we use a mouse model of mild TBI to characterize injury-induced synaptic dysfunction, and examine its progression over the hours to days after trauma. Mild injury consistently caused both locomotor deficits and localized neuroinflammation in piriform and entorhinal cortices, along with reduced olfactory discrimination ability. Using whole-cell recordings to characterize synaptic input onto piriform pyramidal neurons, we found moderate effects on excitatory or inhibitory synaptic function at 48 h after TBI and robust increase in excitatory inputs in slices prepared 1 h after injury. Excitatory increases predominated over inhibitory effects, suggesting that loss of excitatory-inhibitory balance is a common feature of both mild and severe TBI. Our data indicate that mild injury drives rapidly evolving alterations in neural function in the hours following injury, highlighting the need to better characterize the interplay between the primary trauma responses and compensatory effects during this early time period.

Original languageAmerican English
Article number166
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
StatePublished - 12 Apr 2019

Bibliographical note

Publisher Copyright:
© 2019 Witkowski, Gao, Gavsyuk, Maor, DeWalt, Eldred, Mizrahi and Davison.

Keywords

  • Excitatory-inhibitory balance
  • Neuroinflammation
  • Piriform cortex
  • Synapse
  • Traumatic brain injury

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