Subfield‐specific immediate early gene expression associated with hippocampal long‐term potentiation <i>in vivo</i>

French, Pim J.; O’Connor, Vincent; Jones, Matthew W.; Davis, Stephen; Er̀rington, M.L.; Voss, K. L.; Truchet, Bruno; Wotjak, Carsten T.; Stean, Tania O.; Doyère, Valérie; Maroun, Mouna; Laroche, Serge; Bliss, T. V. P.

doi:10.1046/j.0953-816x.2001.01467.x

Cited by 97 publications

(88 citation statements)

References 42 publications

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“…BDNF is clearly being delivered to the CA1 region, and the lack of effect on signal transduction is interesting in this regard. It could be related to differences in activity-dependent gene expression between the CA1 region and dentate gyrus (French et al, 2001). However, there are salient methodological points to this issue.…”

Section: Discussionmentioning

confidence: 93%

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

et al. 2002

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Acute intrahippocampal infusion of brain-derived neurotrophic factor (BDNF) leads to long-term potentiation (BDNF-LTP) of synaptic transmission at medial perforant path3granule cell synapses in the rat dentate gyrus. Endogenous BDNF is implicated in the maintenance of high-frequency stimulation-induced LTP (HFS-LTP). However, the relationship between exogenous BDNF-LTP and HFS-LTP is unclear. First, we found that BDNF-LTP, like HFS-LTP, is associated with enhancement in both synaptic strength and granule cell excitability (EPSP-spike coupling). Second, treatment with a competitive NMDA receptor (NMDAR) antagonist blocked HFS-LTP but had no effect on the development or magnitude of BDNF-LTP. Thus, NMDAR activation is not required for the induction or expression of BDNF-LTP. Formation of stable, late phase HFS-LTP requires mRNA synthesis and is coupled to upregulation of the immediate early gene activityregulated cytoskeleton-associated protein (Arc). Local infusion of the transcription inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion inhibited BDNF-LTP and upregulation of Arc protein expression. ACD applied 2 hr after BDNF infusion had no effect, defining a critical time window of transcription-dependent synaptic strengthening. Finally, the functional role of BDNF-LTP was assessed in occlusion experiments with HFS-LTP. HFS-LTP was induced, and BDNF was infused at time points corresponding to early phase (1 hr) or late phase (4 hr) HFS-LTP. BDNF applied during the early phase led to normal BDNF-LTP. In contrast, BDNF-LTP was completely occluded during the late phase. The results strongly support a role for BDNF in triggering transcription-dependent, late phase LTP in the intact adult brain.

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Section: Discussionmentioning

confidence: 93%

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

et al. 2002

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“…Many of the downregulated ACRGs are IEGs that are highly responsive to neural activity, stress, and arousal and are correlated with synaptic plasticity (Gall et al, 1990;Steward et al, 1998;Guzowski et al, 2000;French et al, 2001). Aspects of memory consolidation are also arousal-dependent (McGaugh, 2000).…”

Section: Behavioral Arousal and Activity-regulated Genesmentioning

confidence: 99%

“…1996; Steward et al, 1998;Guzowski et al, 2000;Bezakova et al, 2001;French et al, 2001). However, Gap-43 appears to be one of the few, or possibly the only, of these yet reported to change with aging and AD (Coleman et al, 1991).…”

Section: Categories Of Acrgsmentioning

confidence: 99%

Gene Microarrays in Hippocampal Aging: Statistical Profiling Identifies Novel Processes Correlated with Cognitive Impairment

et al. 2003

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Gene expression microarrays provide a powerful new tool for studying complex processes such as brain aging. However, inferences from microarray data are often hindered by multiple comparisons, small sample sizes, and uncertain relationships to functional endpoints. Here we sought gene expression correlates of aging-dependent cognitive decline, using statistical profiling of gene microarrays in well powered groups of young, mid-aged, and aged rats (n ϭ 10 per group). Animals were trained on two memory tasks, and the hippocampal CA1 region of each was analyzed on an individual microarray (one chip per animal). Aging-and cognition-related genes were identified by testing each gene by ANOVA (for aging effects) and then by Pearson's test (correlating expression with memory). Genes identified by this algorithm were associated with several phenomena known to be aging-dependent, including inflammation, oxidative stress, altered protein processing, and decreased mitochondrial function, but also with multiple processes not previously linked to functional brain aging. These novel processes included downregulated early response signaling, biosynthesis and activity-regulated synaptogenesis, and upregulated myelin turnover, cholesterol synthesis, lipid and monoamine metabolism, iron utilization, structural reorganization, and intracellular Ca 2ϩ release pathways. Multiple transcriptional regulators and cytokines also were identified. Although most gene expression changes began by mid-life, cognition was not clearly impaired until late life. Collectively, these results suggest a new integrative model of brain aging in which genomic alterations in early adulthood initiate interacting cascades of decreased signaling and synaptic plasticity in neurons, extracellular changes, and increased myelin turnover-fueled inflammation in glia that cumulatively induce agingrelated cognitive impairment.

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“…The evidence came from two main sources: the fact that inhibitors of either protein synthesis (Krug et al 1984;Otani & Abraham 1989;Frey & Morris 1997) or transcription (Nguyen et al 1994) affect the duration of LTP; and the finding that LTP itself induces transcriptional regulation of a variety of genes, including inducible transcription factors (Cole et al 1989;Wisden et al 1990;Abraham et al 1993;Worley et al 1993;French et al 2001) and genes encoding synaptic proteins (e.g. Smirnova et al 1993;Thomas et al 1994Thomas et al , 1996Link et al 1995;Lyford et al 1995;Bramham et al 1996;Hicks et al 1997;Génin et al 2001).…”

Section: Introductionmentioning

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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Subfield‐specific immediate early gene expression associated with hippocampal long‐term potentiation in vivo

Cited by 97 publications

References 42 publications

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

Gene Microarrays in Hippocampal Aging: Statistical Profiling Identifies Novel Processes Correlated with Cognitive Impairment

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

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