Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons

Goldin, Miri; Segal, Menahem

doi:10.1046/j.1460-9568.2003.02694.x

Cited by 120 publications

(97 citation statements)

References 26 publications

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“…In addition to behavioral plasticity, repeated cocaine treatment produces neurochemical (Di Chiara and Imperato, 1988), structural (Robinson and Kolb, 2004) and electrophysiological (Thomas et al, 2001;Borgland et al, 2004) alterations in mesocorticolimbic brain regions. These other forms of neural plasticity are all regulated by the Rascontrolled Raf-MEK-ERK protein kinase signaling cascade Sweatt, 1996, 1997;see Impey et al, 1999;Wu et al, 2001;Mazzucchelli et al, 2002;Goldin and Segal, 2003;Thomas and Huganir, 2004 for review). Thus, it is possible that increased ERK2 signaling due to deletion of ERK1 engages neural circuits that facilitate the neuroadaptations associated with the rewarding and psychomotor sensitizing effects of cocaine.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…To label surface GluR1-containing AMPARs, we first added 5 g͞ml Cy3-conjugated JH1816 (GluR1-N) into neuronal growth media and incubated neurons at 10°C for 20 min. All antibodies were previously described or were acquired commercially: SynGAP (6), NR1 [C-terminal, mAb (40)], PSD-95 (mAb; Upstate, Charlottesville, VA), Bassoon (Stressgen Biotechnologies), GluR1-N [pAb, JH1816 (14)], GluR1-C [JH1710 (40)], microtubule-associated protein 2 (mAb; Sigma), phospho-specific Erk1͞2 [Sigma (16) or Promega (Anti-Active MAPK)], pan-Erk1͞2 (Cell Signaling Technology), and phospho-specific P38 MAPK (Anti-Active P38).…”

Section: Methodsmentioning

confidence: 99%

“…2). To test whether SynGAP may regulate AMPAR trafficking through the MAPK pathway, we examined the regulation of ERK activity in neurons using an antibody that specifically detects phosphorylated, or activated, ERK (16). To observe the maximal range of activation of ERK in cultured neurons, it was necessary to first inhibit the high basal Ras͞ERK activity due to spontaneous synaptic activity in the cultures.…”

Section: Syngap Regulates Synaptic Strength By Altering Ampar Trafficmentioning

confidence: 99%

SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons

Rumbaugh

Adams

Kim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

240

252

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Silent synapses, or excitatory synapses that lack functional ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), are thought to be critical for regulation of neuronal circuits and synaptic plasticity. Here, we report that SynGAP, an excitatory synapse-specific RasGAP, regulates AMPAR trafficking, silent synapse number, and excitatory synaptic transmission in hippocampal and cortical cultured neurons. Overexpression of SynGAP in neurons results in a remarkable depression of AMPAR-mediated miniature excitatory postsynaptic currents, a significant reduction in synaptic AMPAR surface expression, and a decrease in the insertion of AMPARs into the plasma membrane. This change is specific for AMPARs because no change is observed in synaptic NMDA receptor expression or total synapse density. In contrast to these results, synaptic transmission is increased in neurons from SynGAP knockout mice as well as in neuronal cultures treated with SynGAP small interfering RNA. In addition, activation of the extracellular signalregulated kinase, ERK, is significantly decreased in SynGAP-overexpressing neurons, whereas P38 mitogen-activated protein kinase (MAPK) signaling is potentiated. Furthermore, ERK activation is up-regulated in neurons from SynGAP knockout mice, whereas P38 MAPK function is depressed. Taken together, these data suggest that SynGAP plays a critical role in the regulation of neuronal MAPK signaling, AMPAR membrane trafficking, and excitatory synaptic transmission.trafficking ͉ Ras ͉ glutamate ͉ receptor ͉ plasticity E xcitatory synaptic transmission in the mammalian forebrain is primarily mediated by activation of both ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors (1-3). AMPA receptors (AMPARs) mediate the bulk of ion flux during excitatory postsynaptic currents (EPSCs). In contrast, the NMDA receptor is restricted in its ability to pass current because of a voltage-dependent block of its ion channel by magnesium ions, which precludes it from participating in fast synaptic transmission at normal resting membrane potentials. However, when NMDA receptors are activated under depolarized conditions, its high calcium permeability triggers a cascade of signaling events responsible for inducing long-lasting changes in synaptic transmission.Recently, studies have demonstrated that stimuli that elicit long-term potentiation (LTP), a cellular correlate to learning and memory, also result in AMPAR delivery to synapses (4, 5). These studies have led to the idea that AMPARs are highly dynamic and the number of AMPARs at synaptic sites is tightly controlled. With this concept in mind, one can envision that AMPAR concentration at synapses is a major determinant of synaptic ''weight'' or ''strength.'' Thus, molecules and signaling pathways that regulate AMPAR trafficking are likely to directly influence LTP and may be key effectors in neuronal circuit plasticity and information storage.SynGAP, a neuronal specific RasGAP that binds to the PDZ domains of PSD-95 and SAP102 (6), ...

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“…Neuronal morphology, as measured by dendrite arborization and spine density, is modulated by a number of extracellular signals (i.e., neurotrophins, neurotransmitters) (Horch and Katz 2002;Zagrebelsky et al 2005), and signaling via the ERK/MAPK pathway appears to function as a key conduit by which these extracellular cues influence neuronal morphology (Vaillant et al 2002;Goldin and Segal 2003;Kumar et al 2005). Interestingly, ERK/ MAPK signaling has been implicated in both transcriptionally dependent and independent forms of structural plasticity (Dijkhuizen and Ghosh 2005).…”

Section: Msk/mapk and Neuronal Morphologymentioning

confidence: 99%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

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Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1 2/2 mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1 2/2 mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1 2/2 mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1 2/2 animals. MSK1 2/2 mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

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Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons

Cited by 120 publications

References 26 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

SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

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