title: 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 service members 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 LTP, occurring in the CA1 hippocampal Schaffer collateral pathway, is required for both memory formation and retrieval. Surprisingly, ipsilateral Schaffer collateral CA1 LTP evoked by 100 Hz tetanus was enhanced in mice from the 3× closed head injury (3× CHI) treatment group in comparison to LTP in contralateral or 3× Sham CA1 area, and in spite of reduced freezing during contextual fear conditioning at one week following 3× CHI. Electrophysiological activity of CA1 neurons was evaluated with whole-cell patch-clamp recordings. 3× CHI ipsilateral CA1 neurons exhibited significant increases in action potential amplitude and maximum rise and decay slope while the action potential duration was decreased. Recordings of CA1 neuron postsynaptic currents were conducted to detect spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs/sIPSCs) and respective miniature currents (mEPSCs and mIPSCs). In the 3× CHI mice, sEPSCs and sIPSCs in ipsilateral CA1 neurons had an increased frequency of events but decreased amplitudes. In addition, 3× CHI altered the action potential-independent miniature postsynaptic currents. The mEPSCs of ipsilateral CA1 neurons exhibited both an increased frequency of events and larger amplitudes. Moreover, the effect of 3× CHI on mIPSCs was opposite to that of the sIPSCs. Specifically, the frequency of the mIPSCs was decreased while the amplitudes were increased. These results are consistent with a mechanism in which repetitive closed-head injury affects CA1 hippocampal function by promoting a remodeling of excitatory and inhibitory synaptic inputs leading to impairment in hippocampal-dependent tasks.
authors.affiliation: Neuroscience Graduate Program, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States; Department of Anatomy, Physiology and Genetics, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States.
authors.forename: Omar C
authors.initials: OC
authors.lastname: Logue
authors.affiliation: Department of Anatomy, Physiology and Genetics, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Cramer
authors.affiliation: Department of Anatomy, Physiology and Genetics, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Perl
authors.affiliation: Department of Anatomy, Physiology and Genetics, Center for Neuroscience and Regenerative Medicine, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States. Electronic address: zygmunt.galdzicki@usuhs.edu.
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Galdzicki
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005239:Fear; D016489:Head Injuries, Closed / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D011963:Receptors, GABA-A
keywords: Electrophysiology; Hippocampus; Long-term potentiation; Neuroplasticity; Spontaneous excitatory currents; Spontaneous inhibitory currents, fear-conditioning context and cued; Traumatic brain injury