Kinase-dependent modification of dendritic excitability after long-term potentiation

Center for Learning and Memory, University of Texas at Austin, Austin, TX, USA.
The Journal of Physiology (Impact Factor: 5.04). 12/2008; 587(Pt 1):115-25. DOI: 10.1113/jphysiol.2008.158816
Source: PubMed


Patterns of presynaptic activity properly timed with postsynaptic action potential output can not only increase the strength of synaptic inputs but can also increase the excitability of dendritic branches of adult CA1 pyramidal neurons. Here, we examined the role of protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) in the enhancement of dendritic excitability that occurs during theta-burst pairing of presynaptic and postsynaptic firing activity. Using dendritic and somatic whole-cell recordings in rat hippocampal slices, we measured the increase in the amplitude of back-propagating action potentials in the apical dendrite that occurs in parallel with long-term potentiation (LTP) of synaptic inputs. We found that inhibition of the MAPK pathway prevents this enhancement of dendritic excitability using either a weak or strong LTP induction protocol, while synaptic LTP can still be induced by the strong protocol. Both forms of plasticity are blocked by inhibition of PKA and occluded by interfering with cAMP degradation, consistent with a PKA-mediated increase in MAPK activity following induction of LTP. This provides a signalling mechanism for plasticity of dendritic excitability that occurs during neuronal activity and demonstrates the necessity of MAPK activation. Furthermore, this study uncovers an additional contribution of kinase activation to plasticity that may occur during learning.

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    • "p = 0.33, n = 7/7). Then we turned our attention to MEK, which because MAPK cascade is known to be able to integrate coincident signals and to translate the magnitude of signaling into a temporally and spatially graded response [34] and has been previously implicated in learning and memory in behaving animals [35] and shown to be necessary for many forms of synaptic plasticity [34], [36] and dendritic excitability regulation [37] although its precise role is unknown Blocking MEK using 10 uM of U0126 abolished induction of DED (DED = 0.07%±0.3%, p = 0.93). "
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    • "Our observation that neurons expressing Kv4.2S552A show no significant increase in cycling after stimulation indicates that PKA phosphorylation is also required for activity-dependent Kv4.2 cycling at these sites, which has been observed in neuronal culture (Hammond et al., 2008; Kim et al., 2007). Indeed, LTP can be blocked by inhibition of PKA with a PKA inhibitory peptide fragment (Rosenkranz et al., 2009), suggesting that PKA regulation of Kv4.2 channel cycling may play a role in synaptic plasticity. "
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