Related Experiment Videos
Is the Ras-MAPK signalling pathway necessary for long-term memory formation?
P C Orban1, P F Chapman, R Brambilla
1San Raffaele Scientific Institute, Milano, Italy.
Abstract:
Genetic and pharmacological experiments have recently implicated several protein kinase cascades in LTP and memory formation. The small GTPases of the Ras subfamily are activated by multiple extracellular stimuli and, via a complex array of downstream effectors, they control a variety of cellular events that culminate in gene transcription. In the well-characterized Aplysia gill-withdrawal reflex, activation of the Ras-dependent mitogen-activated protein kinase (MAPK) cascade is essential for the long-term, but not the short-term, facilitation process. In addition, in the rodent hippocampus, specific inhibition of the MAPK pathway significantly impairs the induction of LTP, which implicates this signalling cascade in hippocampal-dependent behaviour. Mice that lack the neuronal-specific Ras regulator, Ras-GRF (guanine-releasing factor), have severely impaired LTP in the amygdala and a corresponding deficit in long-term memory for aversive events. The results obtained from these different systems demonstrate the involvement of Ras-dependent signalling in neuronal plasticity and behaviour and raise a number of intriguing questions.
Insights
The Ras signaling pathway, including mitogen-activated protein kinase (MAPK), is crucial for long-term memory and neuronal plasticity. Genetic disruption of Ras regulators impairs learning and memory in animal models.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Signaling
Background:
- Protein kinase cascades are implicated in long-term potentiation (LTP) and memory.
- Small GTPases like Ras regulate cellular events, including gene transcription, in response to stimuli.
Purpose of the Study:
- To investigate the role of Ras-dependent signaling pathways in neuronal plasticity and memory formation.
- To explore the involvement of the mitogen-activated protein kinase (MAPK) cascade in learning and memory.
Main Methods:
- Genetic and pharmacological experiments in Aplysia and rodent models.
- Analysis of LTP induction and memory deficits in genetically modified mice lacking Ras regulators.
Main Results:
- Ras-dependent MAPK cascade activation is essential for long-term facilitation in Aplysia.
- Inhibition of the MAPK pathway impairs LTP induction in rodents.
- Mice lacking Ras-GRF exhibit deficits in amygdala LTP and aversive memory.
Conclusions:
- Ras-dependent signaling pathways are critical for neuronal plasticity, including LTP.
- These pathways play a significant role in learning and memory processes across different species.