Persistent ERK activation maintains learning-induced long-lasting modulation of synaptic connectivity

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Molecular Signaling

Background:

• Olfactory discrimination (OD) training induces lasting synaptic modifications in rat piriform cortex pyramidal neurons.
• Reduced paired-pulse facilitation (PPF), indicative of enhanced synaptic release, is a key modification.
• The molecular mechanisms behind this prolonged synaptic modulation remain largely undescribed.

Purpose of the Study:

• To investigate the role of extracellular signal-regulated kinase (ERK) and protein kinase C (PKC) signaling pathways in learning-induced, long-lasting PPF reduction.
• To determine if these pathways are instrumental in maintaining synaptic modifications after olfactory learning.

Main Methods:

• Administration of MEK inhibitor (PD98059) and PKC inhibitor (GF-109203X) to trained and control rats.
• Measurement of paired-pulse facilitation (PPF) in piriform cortex neurons.
• Assay of activated ERK levels in synaptoneurosomes.

Main Results:

• MEK inhibition (PD98059) abolished PPF differences between trained and control rats, indicating ERK pathway involvement.
• PKC inhibition (GF-109203X) also normalized PPF in trained rats, suggesting PKC is necessary but not sufficient.
• Elevated ERK activation was observed in trained rats, with PPF reduction lagging ERK activation by 2 days.

Conclusions:

• Persistent ERK activation plays a crucial role in maintaining learning-induced PPF reduction for days.
• This compartmental, ERK-dependent synaptic modulation highlights a novel function for ERK in cortical processing.
• Both ERK and PKC signaling are essential for the long-lasting physiological changes in synaptic connectivity following olfactory learning.