title: Investigations on alterations of hippocampal circuit function following mild traumatic brain injury.
abstract: Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological impairments. Two pervasive and disabling symptoms experienced by TBI survivors, memory deficits and a reduction in seizure threshold, are thought to be mediated by TBI-induced hippocampal dysfunction. In order to demonstrate how altered hippocampal circuit function adversely affects behavior after TBI in mice, we employ lateral fluid percussion injury, a commonly used animal model of TBI that recreates many features of human TBI including neuronal cell loss, gliosis, and ionic perturbation. Here we demonstrate a combinatorial method for investigating TBI-induced hippocampal dysfunction. Our approach incorporates multiple ex vivo physiological techniques together with animal behavior and biochemical analysis, in order to analyze post-TBI changes in the hippocampus. We begin with the experimental injury paradigm along with behavioral analysis to assess cognitive disability following TBI. Next, we feature three distinct ex vivo recording techniques: extracellular field potential recording, visualized whole-cell patch-clamping, and voltage sensitive dye recording. Finally, we demonstrate a method for regionally dissecting subregions of the hippocampus that can be useful for detailed analysis of neurochemical and metabolic alterations post-TBI. These methods have been used to examine the alterations in hippocampal circuitry following TBI and to probe the opposing changes in network circuit function that occur in the dentate gyrus and CA1 subregions of the hippocampus (see Figure 1). The ability to analyze the post-TBI changes in each subregion is essential to understanding the underlying mechanisms contributing to TBI-induced behavioral and cognitive deficits. The multi-faceted system outlined here allows investigators to push past characterization of phenomenology induced by a disease state (in this case TBI) and determine the mechanisms responsible for the observed pathology associated with TBI.
authors.affiliation: Division of Neurology, Children's Hospital of Philadelphia, USA
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Brian N
authors.initials: BN
authors.lastname: Johnson
authors.forename: Jaclynn A
authors.initials: JA
authors.lastname: Elkind
authors.forename: Jill M
authors.initials: JM
authors.lastname: See
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xiong
authors.forename: Akiva S
authors.initials: AS
authors.lastname: Cohen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D018408:Patch-Clamp Techniques