title: α-Calcium calmodulin kinase II modulates the temporal structure of hippocampal bursting patterns.
abstract: The alpha calcium calmodulin kinase II (α-CaMKII) is known to play a key role in CA1/CA3 synaptic plasticity, hippocampal place cell stability and spatial learning. Additionally, there is evidence from hippocampal electrophysiological slice studies that this kinase has a role in regulating ion channels that control neuronal excitability. Here, we report in vivo single unit studies, with α-CaMKII mutant mice, in which threonine 305 was replaced with an aspartate (α-CaMKII(T305D) mutants), that indicate that this kinase modulates spike patterns in hippocampal pyramidal neurons. Previous studies showed that α-CaMKII(T305D) mutants have abnormalities in both hippocampal LTP and hippocampal-dependent learning. We found that besides decreased place cell stability, which could be caused by their LTP impairments, the hippocampal CA1 spike patterns of α-CaMKII(T305D) mutants were profoundly abnormal. Although overall firing rate, and overall burst frequency were not significantly altered in these mutants, inter-burst intervals, mean number of intra-burst spikes, ratio of intra-burst spikes to total spikes, and mean intra-burst intervals were significantly altered. In particular, the intra burst intervals of place cells in α-CaMKII(T305D) mutants showed higher variability than controls. These results provide in vivo evidence that besides its well-known function in synaptic plasticity, α-CaMKII, and in particular its inhibitory phosphorylation at threonine 305, also have a role in shaping the temporal structure of hippocampal burst patterns. These results suggest that some of the molecular processes involved in acquiring information may also shape the patterns used to encode this information.
authors.affiliation: Department of Neurobiology, Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jeiwon
authors.initials: J
authors.lastname: Cho
authors.forename: Rushi
authors.initials: R
authors.lastname: Bhatt
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003463:Cues; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D013997:Time Factors
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2