Activation of the extracellular signal-regulated kinases (ERKs) appears to have a critical role in modulating synaptic plasticity in the hippocampus and long-term memory formation. Recent evidences suggest that ERK signalling may be activated in distinct compartments in response to different stimuli, including spines, dendrites and the nucleus. However, a precise knowledge of the downstream effects of ERK activation is still elusive. To investigate the spatial and temporal dynamics of ERK signalling in the hippocampus, we used confocal microscopic immunohistochemistry with a monoclonal antibody specific for phospho-ERK (pERK). Depolarization of hippocampal slices with a hyperkalemic solution (50 mM KCl) induced a strong increase of pERK immunoreactivity in the axon terminals of both mossy fibers in CA3 and Schaffer collaterals in CA1, which were identified by double staining with an antibody against synapsin-I. We next investigated whether long-term potentiation (LTP) -inducing stimuli recruit pERK at synaptic contacts. High-frequency stimulation (HFS) of the mossy fiber-CA3 pathway induced an increase of pERK labeling in mossy fiber terminals. This presynaptic ERK activation showed a six-fold increase 5 minutes after HFS, returned to basal levels after 30 minutes and was completely blocked by the specific inhibitor U0126. HFS of the Schaffer collateral-CA1 pathway resulted in a strong increase of pERK in the dendritic compartment of CA1 pyramidal neurons but not in presynaptic structures. Finally, blocking ERKs activation selectively altered short-term but not long-term synaptic plasticity at mossy fiber-CA3 synapses without modifying basal synaptic transmission. Post-tetanic potentiation induced by a 50 Hz stimulation was selectively increased by the inhibitor at mossy fiber-CA3 synapses, but not at Schaffer collateral-CA1 pathway. These data show that modulation of synaptic strength is dependent on local ERK activation in axon terminals.
Local presynaptic activation of ERKs regulates short-term plasticity in the hippocampus
SASSOE' POGNETTO, Marco;GIUSTETTO, Maurizio
2006-01-01
Abstract
Activation of the extracellular signal-regulated kinases (ERKs) appears to have a critical role in modulating synaptic plasticity in the hippocampus and long-term memory formation. Recent evidences suggest that ERK signalling may be activated in distinct compartments in response to different stimuli, including spines, dendrites and the nucleus. However, a precise knowledge of the downstream effects of ERK activation is still elusive. To investigate the spatial and temporal dynamics of ERK signalling in the hippocampus, we used confocal microscopic immunohistochemistry with a monoclonal antibody specific for phospho-ERK (pERK). Depolarization of hippocampal slices with a hyperkalemic solution (50 mM KCl) induced a strong increase of pERK immunoreactivity in the axon terminals of both mossy fibers in CA3 and Schaffer collaterals in CA1, which were identified by double staining with an antibody against synapsin-I. We next investigated whether long-term potentiation (LTP) -inducing stimuli recruit pERK at synaptic contacts. High-frequency stimulation (HFS) of the mossy fiber-CA3 pathway induced an increase of pERK labeling in mossy fiber terminals. This presynaptic ERK activation showed a six-fold increase 5 minutes after HFS, returned to basal levels after 30 minutes and was completely blocked by the specific inhibitor U0126. HFS of the Schaffer collateral-CA1 pathway resulted in a strong increase of pERK in the dendritic compartment of CA1 pyramidal neurons but not in presynaptic structures. Finally, blocking ERKs activation selectively altered short-term but not long-term synaptic plasticity at mossy fiber-CA3 synapses without modifying basal synaptic transmission. Post-tetanic potentiation induced by a 50 Hz stimulation was selectively increased by the inhibitor at mossy fiber-CA3 synapses, but not at Schaffer collateral-CA1 pathway. These data show that modulation of synaptic strength is dependent on local ERK activation in axon terminals.
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