Is the Ras-MAPK signalling pathway necessary for long-term memory formation?

Genetic and pharmacological experiments have recently implicated several pr otein kinase cascades in LTP and memory formation,The small GTPases of the pas subfamily are activated by multiple extracellular stimuli and, via a co mplex array of downstream effectors, they control a variety of cellular eve nts that culminate in gene transcription. In the well-characterized Aplysia gill-withdrawal reflex, activation of the pas-dependent mitogen-activated protein kinase (MAPK) cascade is essential for the long-term, but not the s hort-term, facilitation process, In addition, in the rodent hippocampus, sp ecific inhibition of the MAPK pathway significantly impairs the induction o f LTP, which implicates this signalling cascade in hippocampal-dependent be haviour, Mice that lack the neuronal-specific pas regulator, Ras-GRF (guani ne-releasing factor), have severely impaired LTP in the amygdala and a corr esponding deficit in long-term memory for aversive events. The results obta ined from these different systems demonstrate the involvement of pas-depend ent signalling in neuronal plasticity and behaviour and raise a number of i ntriguing questions.