A role for the Ras signalling pathway in synaptic transmission and long-term memory

Brambilla, Riccardo; Gnesutta, Nerina; Minichiello, Liliana; White, Gail L.; Roylance, Alistair J.; Herron, Caroline E.; Ramsey, Mike; Wolfer, David P; Cestari, Vincenzo; Rossi-Arnaud, Clelia; Grant, Seth G. N.; Chapman, Paul F.; Lipp, Hans Peter; Sturani, E.; Klein, Rüdiger

doi:10.1038/36849

Cited by 440 publications

(262 citation statements)

References 30 publications

Supporting

Mentioning

241

Contrasting

Unclassified

Order By: Relevance

“…A similar increase in the 42-kDa, but not 44-kDa, protein had been reported by English and Sweatt [121] after induction of long-term potentiation in hippocampal CA1. Thus it is difficult to reconcile that mutant mice lacking Ras-GRF, a small G-protein family member, did not show abnormalities in hippocampal synaptic plasticity or hippocampus-dependent learning [122]. However, longterm plasticity is abnormal in the amygdala, and longterm memory is reduced for contextual or cued conditioning.…”

Section: Mapk Cascadementioning

confidence: 94%

Protein kinases: which one is the memory molecule?

Micheau

Riedel

1999

Cellular and Molecular Life Sciences (CMLS)

125

View full text Add to dashboard Cite

Encoding of new experiences is likely to induce activity-dependent modifications in the brain. Studies in organisms far apart on the phylogenetic scale have shown that similar, sometimes identical, signal transduction pathways subserve plasticity in neuronal systems, and they may play pivotal roles in the formation of long-term memories. It has become evident that phosphorylation/dephosphorylation reactions are critical for the initiation of cellular mechanisms that embody, retain and modify information in neural circuits. Although physiological investigations on synaptic plasticity have had a major impact, we have concentrated our review on behavioural studies that provide direct or indirect evidence for a role of kinases in mechanisms underlying memory formation. From these, it appears that the learning event induces activation of a variety of kinases with specific time courses. For instance, the calcium/calmodulin-dependent protein kinase II seems to participate in an early phase of memory formation. Apparently, activation of both protein tyrosine kinases and mitogen-activated protein kinases is required for much longer and may thus have a particular function during transformation from short-term into long-term memory. Quite different time courses appear for protein kinase C (PKC) and protein kinase A (PKA), which may function at two different time points, shortly after training and again much later. This suggests that PKC and PKA might play a role at early and late stages of memory formation. However, we have considered some examples showing that these signalling pathways do not function in isolation but rather interact in an intricate intracellular network. This is indicative of a more complex contribution of each kinase to the fine tuning of encoding and information processing. To decipher this complexity, pharmacological, biochemical and genetic investigations are more than ever necessary to unravel the role of each kinase in the syntax of learning and memory formation.

show abstract

Section: Mapk Cascadementioning

confidence: 94%

Protein kinases: which one is the memory molecule?

Micheau

Riedel

1999

Cellular and Molecular Life Sciences (CMLS)

125

View full text Add to dashboard Cite

show abstract

“…Additional support of the involvement of Ras-dependent signalling came from another strain lacking the neuronal specific Ras exchange factor RasGRF. In contrast with NF1 mice, RasGRF −/− mice are viable and fertile and do not manifest gross morphological alterations in overall brain organisation [53]. Yet Ras-GRF KO mice are severely impaired in amygdala-dependent behavioural tasks, such as operant and classical conditioning tests.…”

Section: Genetic Experimentsmentioning

confidence: 98%

Ras-related and MAPK signalling in neuronal plasticity and memory formation

Mazzucchelli¹,

Brambilla²

2000

CMLS, Cell. Mol. Life Sci.

139

View full text Add to dashboard Cite

Ras-related guanosine triphosphatases (GTPases) couple receptor activity to a number of intracellular signalling events culminating in the control of cell morphology and gene transcription. In culture cells, the best-understood Ras-dependent signalling pathway involves the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) cascade. A growing body of evidence has recently been accumulating to suggest a crucial role of Ras and MAPK signalling in neuronal functions connected to synaptic plasticity. In the present review article we discuss the experimental basis supporting the notion that the Ras/MAPK pathway interacts with other synaptic mechanisms to regulate invertebrate and vertebrate behavioural responses such as those implicated in learning and memory processes.

show abstract

“…Consequently, further progress may be made by examining the role of imprinted genes in adult brain functions such as discrete aspects of cognition. This has been reviewed elsewhere (Isles & Wilkinson 2000), but in summary animal studies have so far demonstrated that imprinted genes impact on behavioural flexibility (Davies et al 2005a) and several different aspects of memory functioning, including emotional (Brambilla et al 1997), context dependent (Jiang et al 1998) and spatial (Muscatelli et al 2000). Studies on human mental dysfunction indicate a similar array of possible roles for imprinted genes in cognitive functioning (reviewed in Davies et al 2001), including behavioural flexibility (Skuse et al 1997), spatial memory (Curfs et al 1991) and mental rotation (Bishop et al 2000), and what can be broadly described as 'social cognition' (Cook et al 1997;Skuse et al 1997;Boer et al 2002).…”

Section: Sex-biased Dispersal Intragenomic Conflict and Social Behavmentioning

confidence: 99%

Genomic imprinting and the social brain

Isles

Davies

Wilkinson

2006

Phil. Trans. R. Soc. B

109

View full text Add to dashboard Cite

Genomic imprinting refers to the parent-of-origin-specific epigenetic marking of a number of genes. This epigenetic mark leads to a bias in expression between maternally and paternally inherited imprinted genes, that in some cases results in monoallelic expression from one parental allele. Genomic imprinting is often thought to have evolved as a consequence of the intragenomic conflict between the parental alleles that occurs whenever there is an asymmetry of relatedness. The two main examples of asymmetry of relatedness are when there is partiality of parental investment in offspring (as is the case for placental mammals, where there is also the possibility of extended postnatal care by one parent), and in social groups where there is a sex-biased dispersal. From this evolutionary starting point, it is predicted that, at the behavioural level, imprinted genes will influence what can broadly be termed bonding and social behaviour. We examine the animal and human literature for examples of imprinted genes mediating these behaviours, and divide them into two general classes. Firstly, mother-offspring interactions (suckling, attachment and maternal behaviours) that are predicted to occur when partiality in parental investment in early postnatal offspring occurs; and secondly, adult social interactions, when there is an asymmetry of relatedness in social groups. Finally, we return to the evolutionary theory and examine whether there is a pattern of behavioural functions mediated by imprinted genes emerging from the limited data, and also whether any tangible predictions can be made with regards to the direction of action of genes of maternal or paternal origin.

show abstract

A role for the Ras signalling pathway in synaptic transmission and long-term memory

Cited by 440 publications

References 30 publications

Protein kinases: which one is the memory molecule?

Protein kinases: which one is the memory molecule?

Ras-related and MAPK signalling in neuronal plasticity and memory formation

Genomic imprinting and the social brain

Contact Info

Product

Resources

About