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

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.