Abstract
Cyclin-dependent kinase-like 2 (Cdkl2) is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the cerebral cortex, entorhinal cortex, hippocampus, amygdala, and dorsal thalamus. The extremely high Cdkl2 expression in these regions suggests that it has a role in cognition and emotion. Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and neuropsychiatric disorders in humans. To elucidate the physiologic role of Cdkl2, we behaviorally analyzed Cdkl2LacZ/LacZ mice lacking Cdkl2. Cdkl2LacZ/LacZ mice had reduced latencies to enter the dark compartment after electric footshock in an inhibitory avoidance task and attenuated contextual fear responses when exposed to mild training conditions. Hippocampal spatial learning in the Morris water maze was slightly anomalous with mice exhibiting an abnormal swimming pattern. The aversive response in a two-way avoidance task was slightly, but not significantly, enhanced. On the other hand, Cdkl2LacZ/LacZ mice did not exhibit altered sensitivity to aversive stimuli, such as electric footshock and heat, or deficits in the elevated plus maze or rotating rod test. These findings suggest that Cdkl2 is involved in cognitive function and provide in vivo evidence for the function of Cdkl family kinases expressed in terminally differentiated neurons in mice.
Highlights
Current understanding of the molecular mechanisms of synaptic plasticity emphasizes the important role of phosphorylation of synaptic substrates, including glutamate receptors (Lee, 2006)
As previously reported in Cdkl2LacZ/+ mice (Sassa et al, 2004), the LacZ-reporter was expressed in neurons in various brain regions, including the olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, thalamic nuclei, amygdaloid nuclei, entorhinal cortex, and deep cerebellar nuclei (Figure 3)
We generated Cdkl2LacZ/ LacZ mice to investigate the role of Cyclin-dependent kinase-like 2 (Cdkl2) in brain function
Summary
Current understanding of the molecular mechanisms of synaptic plasticity emphasizes the important role of phosphorylation of synaptic substrates, including glutamate receptors (Lee, 2006). Activation of the MAPK signaling cascade is involved in long-term facilitation of the sensory to motor synapse in Aplysia and in hippocampal long-term potentiation, water maze learning, and contextual fear conditioning in mammals (Martin et al, 1997; Atkins et al, 1998; Selcher et al, 1999, 2003; Satoh et al, 2007). This evidence suggests that the Cdkl kinase family might be involved in behavioral modification, activity-dependent synaptic plasticity, and learning
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