title: Selective loss of hippocampal long-term potentiation, but not depression, following fluid percussion injury.
abstract: We investigated the early effects of in vivo fluid percussion injury (FPI) on hippocampal synaptic potentials and excitability. In vitro field potential recordings and immunocytochemistry were performed in the CA1 region in slices from naïve, post-FPI, or sham-operated rats. The following electrophysiological and morphological parameters were affected following FPI: (1) threshold for population spike generation was increased suggesting that post-FPI neurons were hypoexcitable; (2) long-term potentiation (LTP) could not be induced in injured hippocampi; (3) GFAP and inducible NO synthase (iNOS) immunoreactivity were enhanced post-FPI; and (4) following injury, synaptophysin immunoreactivity was enhanced in CA1 stratum radiatum. The effects of FPI on synaptic plasticity were LTP-specific, since long-term depression (LTD) could be equally induced and maintained in post-FPI, sham-operated and control slices. Sham-operated slices were characterized by synaptic excitability indistinguishable from naïve controls, but displayed decreased ability for LTP production and expressed high levels of iNOS. We conclude that FPI causes a selective loss of LTP, possibly due to a previous potentiation induced by trauma as reflected by the increased expression of synaptic proteins. Sham surgical procedures were, however, not without effects on long-term potentiation itself; the latter effects appear to be mediated by an increased production of NO. Our study demonstrates for the first time that hippocampal slices can be used to investigate the correlates of in vivo FPI. Furthermore, we describe LTP-specific deficits in post-traumatic brain injury, suggesting that FPI can selectively erase one of the two main NMDA-dependent forms of synaptic plasticity in the hippocampus.
authors.affiliation: Department of Neurological Surgery, University of Washington, School of Medicine, Seattle, WA 98104, USA.
authors.forename: R
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: D O
authors.initials: DO
authors.lastname: Maris
authors.forename: M S
authors.initials: MS
authors.lastname: Grady
authors.forename: H R
authors.initials: HR
authors.lastname: Winn
authors.forename: D
authors.initials: D
authors.lastname: Janigro
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D014949:Wounds, Nonpenetrating / Q000473:pathology / Q000503:physiopathology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat