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Differential effects of αCaMKII mutation on hippocampal learning and changes in intrinsic neuronal excitability
Author(s) -
Ohno Masuo,
Sametsky Evgeny A.,
Silva Alcino J.,
Disterhoft John F.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04746.x
Subject(s) - neuroscience , hippocampal formation , morris water navigation task , afterhyperpolarization , autophosphorylation , synaptic plasticity , water maze , hippocampus , schaffer collateral , chemistry , biology , kinase , protein kinase a , microbiology and biotechnology , receptor , inhibitory postsynaptic potential , excitatory postsynaptic potential , biochemistry
α‐Calcium/calmodulin‐dependent kinase II (αCaMKII) is central to synaptic plasticity but it remains unclear whether this kinase contributes to neuronal excitability changes, which are a cellular correlate of learning. Using knock‐in mice with a targeted T286A mutation that prevents the autophosphorylation of αCaMKII (αCaMKII T286A ), we studied the role of αCaMKII signaling in regulating hippocampal neuronal excitability during hippocampus‐dependent spatial learning in the Morris water maze. Wild‐type control mice showed increased excitability of CA1 pyramidal neurons, as assessed by a reduction in the postburst afterhyperpolarization (AHP), after spatial training in the water maze. Importantly, wild‐type mice did not show AHP changes when they were exposed to the water maze without the escape platform and swam the same amount of time as the trained mice (swim controls), thus manifesting learning‐specific increases in hippocampal CA1 excitability associated with spatial training. Meanwhile, αCaMKII T286A mice showed impairments in spatial learning but exhibited reduced levels of AHP that were similar to wild‐type controls after water‐maze training. Notably, both trained and swim‐control groups of αCaMKII T286A mutants showed similar increased excitability, indicating that swimming by itself is enough to induce changes in excitability in the absence of normal αCaMKII function. This result demonstrates dissociation of αCaMKII‐independent changes in intrinsic neuron excitability from learning and synaptic plasticity mechanisms, suggesting that increases in excitability per se are not perfectly correlated with learning. Our findings suggest that αCaMKII signaling may function to suppress learning‐unrelated changes during training, thereby allowing hippocampal CA1 neurons to increase their excitability appropriately for encoding spatial memories.