Previous studies demonstrated that α-CaMKII has a role in the stability of hippocampal place fields: Transgenic mice that express a mutated Ca2+
-independent form of α-CaMKII show place cells that are both less precise and less stable 
. Similarly, studies of mice with a mutation that substituted threonine 286 for alanine (α-CaMKII T286A) also revealed unstable place cells 
. Both of these α-CaMKII mutations impaired hippocampal CA1 N-Methyl-D-Aspartate Receptor (NMDAR) dependent LTP as well as hippocampal-dependent learning (e.g. spatial learning)
. These and other results indicated that hippocampal CA1 LTP is required for the stability of place cells 
. Here, we describe in vivo
electrophysiological studies suggesting that besides a role in the stability of place fields, α-CaMKII is also implicated in shaping bursting patterns.
Besides unstable place fields with lower spatial coherence, α-CaMKII T305D mutant mice show dramatic changes in both the intra-burst and inter-burst properties of hippocampal place cells. Comparisons between T305D and WT groups showed that although the frequency of bursts did not differ significantly between the two groups, burst length (number of spikes per burst), average inter-burst intervals, and average intra burst intervals were altered in the mutants.
In addition, both inter-burst and intra-burst intervals were more variable in place cells of T305D mice, demonstrating that this mutation introduced high variability in the temporal structure of spike patterns. Spatial selectivity (elevation in firing rate within the place field) appeared to be lower in the T305D mutants, but this did not reach statistical significance. The variability in spike patterns of T305D mutants may have also affected other properties of spike bursts, perhaps accounting for the decreased spatial coherence and larger place fields of T305D mice. Thus, it is possible that the greater variability of bursting patterns of T305D mice contributed to their spatial learning deficits 
What could be the mechanism responsible for the changes of bursting patterns in T305D mice? Electrophysiological studies in brain slices indicated that this kinase modulates intrinsic excitability by regulating various ion currents. CaMKII may phosphorylate and regulate T-type Ca2+
channels thought to modulate the initiation of dendritic and somatic Ca2+
spikes involved in shaping spike patterns 
. There is also a significant amount of evidence that implicates CaMKII in the modulation of A currents. CaMKII phosphorylates synapse dependent protein 97 (SAP97), and this phosphorylation regulates the post-synaptic density and dendritic localization of a key constituent of A currents (Kv4.2) 
. A-type potassium currents (and Kv4.2) were implicated in the regulation of dendritic excitability and plasticity 
. These findings are consistent with results from Drosophila showing that CaMKII inhibition with KN-62 or KN-93 caused a significantly decreased A-type current and resulted in abnormal firing patterns, including increased variability in spike frequency, inter-spike-interval, spike duration and amplitude 
. Hippocampal neurons from α-CaMKII null mutants and rat neurons treated with a CaMKII inhibitor showed increased neuronal excitability and preponderance for both spontaneous and evoked seizures 
. Cultured hippocampal neurons treated with a CaMKII inhibitor showed abnormal spike rates 
CaMKII is also thought to modulate the slow component of post-burst afterhyperpolarization (sAHP), a current known to shape spike patterns, since α-CaMKII T286A mutant mice showed a decrease in hippocampal sAHP following tetanic synaptic stimulation
. CaMKII may also modulate (directly or indirectly) the slowly activating h current, a key regulatory component of neuronal firing. Postsynaptic theta-burst firing can decrease neuronal excitability in a h-channel dependent manner. This decrease in excitability is also CaMKII-dependent, since an inhibitor of this kinase prevents it 
. CaMKII-mediated phosphorylation of high-conductance, Ca2+
-activated and voltage-gated (BK) channels is known to increase channel activity, and these channels have a key role in neuronal firing 
. Additionally, there is also evidence that CaMKII modulates the expression and localization of G-protein-gated inwardly rectifying potassium (GIRK) channels 
. Thus, CaMKII regulates a number of currents that are known to affect neuronal excitability and modulate spike patterns. However, prior to the present study there was little in vivo
evidence demonstrating that this kinase had a role in shaping spike patterns.
Our results provide direct in vivo evidence that besides a role in the stability of hippocampal place fields (likely due to its involvement in the induction of LTP), α-CaMKII also modulates the temporal structure of spike patterns. Thus, the results presented here suggest that some of the molecular processes involved in acquiring information may also shape the patterns used to encode this information.