A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

Selcher, Joel C.; Atkins, Coleen M.; Trzaskos, James M.; Paylor, Richard; Sweatt, J. David

doi:10.1101/lm.6.5.478

Cited by 318 publications

(257 citation statements)

References 45 publications

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“…It has an IC50 of 180 nM for MEK1 and 220 nM for MEK2 (Favata et al, 1998). The dose of SL327 used in the present study (40 mg/kg) was chosen because it has been shown to effectively block ERK activation in vivo (Selcher et al, 1999) and we have found it to be effective at reducing psychostimulant-evoked IEG expression without altering the acute locomotor activating effects of psychostimulants and data not shown).…”

Section: Drugsmentioning

confidence: 99%

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

Ferguson

Fasano

Yang

et al. 2006

Neuropsychopharmacol

110

100

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The ability of cocaine to produce lasting neural adaptations in mesocorticolimbic brain regions is thought to promote drug seeking and facilitate addiction in humans. The Ras-controlled Raf-MEK-ERK protein kinase signaling cascade has been implicated in the behavioral and neurobiological actions of cocaine in animals. However, these pharmacological studies have not been able to determine the specific role of the two predominant isoforms of ERK (ERK1 and ERK2) in these processes. We report here that deletion of the ERK1 isoform, which leads to increased ERK2 stimulus-dependent signaling, facilitates the development of cocaine-induced psychomotor sensitization and the acquisition of a cocaine conditioned place preference. Conversely, pharmacological blockade of ERK signaling attenuates the development of psychomotor sensitization to cocaine. Finally, cocaine-evoked gene expression in mesocorticolimbic brain regions is potentiated in ERK1-deficient mice. Thus, alterations in ERK signaling influence both the neurobiological impact of cocaine and its ability to produce enduring forms of drug experience-dependent behavioral plasticity. Our results suggest that enhanced ERK2 signaling following repeated drug exposure may facilitate the development of forms of cocaine-induced plasticity that contribute to addiction.

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Section: Drugsmentioning

confidence: 99%

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

Ferguson

Fasano

Yang

et al. 2006

Neuropsychopharmacol

110

100

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“…Within a few years, several groups had shown that MAPK/ERK is activated in the hippocampus and is required for a variety of hippocampal-dependent forms of learning (reviewed in Impey et al 1999;Sweatt 2001). For example, inhibition of the upstream kinase MEK produces deficits in memory for cued and contextual fear associations (Atkins et al 1998) and in spatial memory (Blum et al 1999;Selcher et al 1999). Similar results have been obtained in the lateral nucleus of the amygdala in the consolidation of fear memory (Schafe et al 2000) where zif268 is also activated (Malkani & Rosen 2000;Hall et al 2001).…”

Section: The Mapk/erk Signalling Pathway Zif268 Transcription and Ltpmentioning

confidence: 99%

MAPK, CREB andzif268are all required for the consolidation of recognition memory

Bozon

Kelly

Josselyn

et al. 2003

Phil. Trans. R. Soc. Lond. B

285

211

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There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/ extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response elementbinding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

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“…In rodents, behavior and memory, including spatial learning [14,15] and conditioned place preference [16] , appear to involve the ERK/MAPK pathway.…”

Section: Introductionmentioning

confidence: 99%

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

Xue

Yuan

et al. 2009

Acta Pharmacol Sin

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Aim: The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd. Methods: The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF). Results: When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus. Conclusion: Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.

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A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

Cited by 318 publications

References 45 publications

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

MAPK, CREB andzif268are all required for the consolidation of recognition memory

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

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