Abstract
Although classically studied as regulators of cell proliferation and differentiation, mitogen-activated protein kinases (MAPKs) are highly expressed in post-mitotic neurons of the adult nervous system. We have begun investigating the potential role of MAPKs in the regulation of synaptic plasticity in mature neurons. In particular, we have studied the regulation of two MAPK isoforms, p44 and p42 MAPK, in hippocampal long term potentiation (LTP), a system widely studied as a model for the cellular basis of learning and memory. We have found that p42 MAPK, but not p44 MAPK, is activated in area CA1 following direct stimulation of two required components of the LTP induction cascades: protein kinase C and the N-methyl--aspartate (NMDA) subtype of glutamate receptor. Furthermore, we have demonstrated that p42 MAPK, but not p44 MAPK, is activated in area CA1 in response to LTP-inducing high frequency stimulation and that this activation requires NMDA receptor stimulation. These data demonstrate that p42 MAPK can be regulated in an activity-dependent manner in the hippocampus and identify it as a potential component of the LTP induction cascades in area CA1. Such observations suggest that p42 MAPK might be an important regulator of synaptic plasticity in post-mitotic neurons.
Highlights
N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, postsynaptic calcium flux, and activation of several protein kinase cascades
Mitogen-activated protein kinases (MAPKs) are expressed in dendrites and somas of pyramidal neurons of the adult nervous system [5], a localization that suggests a role for MAPK in postsynaptic functions
We first observed that p42 MAPK, but not p44 MAPK, is activated following direct stimulation of two required components of the long term potentiation (LTP) induction cascades, namely protein kinase C (PKC) and NMDA receptors
Summary
N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, postsynaptic calcium flux, and activation of several protein kinase cascades (reviewed in Ref. 2). Several studies have demonstrated that MAPKs are activated following stimulation of neurotransmitter receptors, protein kinase C (PKC), and neuronal growth factor receptors (6 –12). P42 MAPK, but Not p44 MAPK, Is Activated in Area CA1 following Stimulation of Protein Kinase C—Several lines of evidence demonstrate that PKC is a critical component of the LTP induction cascades in area CA1 of the hippocampus.
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