title: Mechanisms underlying the inability to induce area CA1 LTP in the mouse after traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a significant health issue that often causes enduring cognitive deficits, in particular memory dysfunction. The hippocampus, a structure crucial in learning and memory, is frequently damaged during TBI. Since long-term potentiation (LTP) is the leading cellular model underlying learning and memory, this study was undertaken to examine how injury affects area CA1 LTP in mice using lateral fluid percussion injury (FPI). Brain slices derived from FPI animals demonstrated an inability to induce LTP in area CA1 7 days postinjury. However, area CA1 long-term depression could be induced in neurons 7 days postinjury, demonstrating that some forms of synaptic plasticity can still be elicited. Using a multi-disciplined approach, potential mechanisms underlying the inability to induce and maintain area CA1 LTP were investigated. This study demonstrates that injury leads to significantly smaller N-methyl-D-aspartate potentials and glutamate-induced excitatory currents, increased dendritic spine size, and decreased expression of alpha-calcium calmodulin kinase II. These findings may underlie the injury-induced lack of LTP and thus, contribute to cognitive impairments often associated with TBI. Furthermore, these results provide attractive sites for potential therapeutic intervention directed toward alleviating the devastating consequences of human TBI.
authors.affiliation: Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. eschwarz@mail.med.upenn.edu
authors.forename: E
authors.initials: E
authors.lastname: Schwarzbach
authors.forename: D P
authors.initials: DP
authors.lastname: Bonislawski
authors.forename: G
authors.initials: G
authors.lastname: Xiong
authors.forename: A S
authors.initials: AS
authors.lastname: Cohen
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009924:Organ Culture Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases