Alterations of Functional Properties of Hippocampal Networks Following Repetitive Closed-Head Injury
Abstract
Traumatic brain injury (TBI) is the leading cause of death for persons under the age of 45. Military Servicemembers who have served on multiple combat deployments, and contact-sport athletes, are at particular risk of sustaining repetitive TBI (rTBI). Cognitive and behavioral deficits resulting from rTBI are well documented. Optimal associative long-term potentiation (LTP), occurring in the CA1 hippocampal Schaffer collateral pathway, is required for both memory formation and retrieval. Utilizing our mouse model of rTBI, we hypothesized that a triple closed-head injury (3X CHI) will trigger alterations in hippocampal function to include inhibition of LTP and attenuation of electrical activity. One week after 3X CHI, extracellular recordings were performed to evoke Schaffer collateral LTP in the CA1 area. Surprisingly, ipsilateral CA1 LTP was enhanced in mice from the 3X CHI treatment group. The intrinsic properties of CA1 neurons were evaluated with whole-cell patch-clamp recordings. 3X CHI ipsilateral CA1 neurons exhibited significant increases in action potential amplitude, maximum rise slope, and maximum decay slope, while the action potential was decreased. Recordings of CA1 neuron postsynaptic currents were conducted to detect spontaneous excitatory (EPSCs) and inhibitory (IPSCs) and respective miniature currents (mEPSCs and mIPSCs). In the 3X CHI mice, the sEPSCs and sIPSCs of ipsilateral CA1 neurons had an increased frequency of events but decreased peak amplitudes. Conversely, 3X CHI altered the action potential-independent miniature postsynaptic currents in a different manner. The mEPSCs of ipsilateral CA1 neurons displayed both an increased frequency of events and larger peak amplitudes. Moreover, the effect of 3X CHI on mIPSCs was opposite to that of the sIPSCs. That is, the frequency of events in the mIPSCs was decreased, while the peak amplitudes were increased. These results are contrary to our original hypothesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 24, 2014
- Accession Number
- AD1127825
Entities
People
- Omar Logue
Organizations
- Uniformed Services University of the Health Sciences