The Experts below are selected from a list of 25791 Experts worldwide ranked by ideXlab platform
Mike Dragunow - One of the best experts on this subject based on the ideXlab platform.
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Immediate Early Gene transcription and synaptic modulation.
Journal of neuroscience research, 1999Co-Authors: M. Walton, Wickliffe C. Abraham, P. Lawlor, C. Henderson, Sara E. Mason-parker, David K. Bilkey, Mike DragunowAbstract:Long-term changes in Gene expression appear to be critical to the formation of memory, but little is known about its stimulus- transcription coupling. Numerous studies in the last decade, by focusing on unraveling this signal transduction pathway, have investigated the potential role of the Immediate-Early Genes in this process. The krox family of Immediate-Early Gene proteins are of particular interest because they may be involved in stabilizing the synaptic modifications that underlie hippocampal long-term potentiation (LTP). A potential upstream mediator of krox induction is cyclic AMP-responsive element binding protein (CREB), a posttranslationally activated transcription factor that has been implicated in numerous memory paradigms. In this study we investigated whether the activation of CREB by phosphorylation may have a role in the development of rat perforant- path-stimulated LTP and associated dentate granule cell krox-24 mRNA expression. Contrary to what was expected, we failed to show any difference in the levels of phosphorylated CREB after LTP or following endogenous synaptic facilitation stimulated by novelty. Using these same model systems we also investigated the protein levels of brain- derived neurotrophic factor (BDNF), another Immediate-Early Gene that is induced following a durable form of LTP. However, BDNF protein was not induced within the hippocampus after LTP and was transiently decreased following novel environmental stimulation. J. Neurosci. Res. 58:96–106, 1999. © 1999 Wiley-Liss, Inc.
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Immediate Early Gene expression associated with the persistence of heterosynaptic long-term depression in the hippocampus
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Wickliffe C. Abraham, P. Lawlor, Brian R. Christie, Barbara Logan, Mike DragunowAbstract:Abstract Long-term depression (LTD) of synaptic efficacy is likely to be as important in memory processing as the more well-known long-term potentiation (LTP). The case for LTD serving as a memory mechanism, however, requires that it be shown to persist across days or weeks at least. Here we examined the persistence of heterosynaptic LTD in the medial and lateral perforant path inputs to the dentate gyrus in awake rats and correlated this persistence with the degree of Immediate Early Gene expression as assessed immunohistochemically. Rats were chronically implanted with separate stimulating electrodes in the medial and lateral perforant paths and an extracellular field potential recording electrode in the dentate hilus. After recovery from surgery, either the medial or the lateral perforant path was tetanized with 400-Hz trains, and homosynaptic LTP and heterosynaptic LTD were followed across time. Heterosynaptic LTD was shown to occur readily in awake animals and to persist across days or weeks, depending on the stimulation protocol. The persistence of LTD and LTP was highly correlated within animals. Additional animals, given the same tetanization protocols, showed that the greatest Immediate Early Gene expression occurred following that protocol which consistently gave the longest-lasting LTP and LTD. These data support the proposed role of LTD in memory processing but question whether Immediate Early Genes are important for the persistence of LTP, LTD, or both.
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MK-801 Does Not Attenuate Immediate-Early Gene Expression Following an Amygdala Afterdischarge
Experimental neurology, 1994Co-Authors: Paul E. Hughes, Kerin Singleton, Mike DragunowAbstract:Abstract It has been suggested that the increased transient expression of Immediate-Early Gene transcription factors seen in nerve cells following an afterdischarge may initiate longer lasting or permanent changes in Gene expression which underly the development of kindling. Since the development of kindling is sensitive to pharmacological blockade of the N -methyl- d -aspartate receptor, we tested whether the increased expression of the Immediate-Early Genes c-fos, jun-B, c-jun, krox-20 , and krox-24 following a kindling afterdischarge was also sensitive to N -methyl- d -aspartate receptor blockade by MK-801. In this report we demonstrate that all five Immediate-Early Genes are induced by an amygdala afterdischarge. N -methyl- d -aspartate receptor blockade by a dose of MK-801 that significantly retards the development of amygdala kindling failed to attenuate Immediate-Early Gene expression. These results suggest that although expression of these five Immediate-Early Genes occurs after an amygdala afterdischarge their expression is not involved in the N -methyl- d -aspartate receptor-mediated component of amygdala kindling.
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Correlations between Immediate Early Gene induction and the persistence of long-term potentiation
Neuroscience, 1993Co-Authors: Wickliffe C. Abraham, S.e. Mason, Jerome Demmer, Joanna M. Williams, C.l. Richardson, P. Lawlor, Warren P. Tate, Mike DragunowAbstract:Abstract The duration of long-term potentiation in the dentate gyrus of awake rats was examined following systematic manipulation of the number of stimulus trains delivered. This was correlated with the induction of Immediate Early Genes in separate groups of animals given identical stimulus regimes. Following 10 trains of stimulation, long-term potentiation decayed with a time constant of up to several days (long-term potentiation 2), and this correlated with the appearance of an increase in the messenger RNA and protein levels of zif/268. Increasing the number of stimulus trains resulted in a greater probability of eliciting long-term potentiation with a time constant of several weeks (long-term potentiation 3), as well as increasing the induction of zif/268, c-Jun, Jun-B, Jun-D and Fos-related proteins. When 10 trains were delivered repeatedly on up to five consecutive days, only the zif/268 protein levels showed associated changes. These data provide support for the hypothesis that long-term potentiation 3 involves mechanisms additional to those for long-term potentiation 2. One possible mechanism is altered Gene expression, initiated by Immediate Early Gene transcription factors such as zif/268 and possibly homo- or heterodimers of Fos and Jun family members, that then contributes to the stabilization or maintenance of long-term potentiation 3.
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Brain-derived neurotrophic factor is induced as an Immediate Early Gene following N-methyl-d-aspartate receptor activation
Neuroscience, 1993Co-Authors: Paul E. Hughes, Erica J. Beilharz, Peter D. Gluckman, Mike DragunowAbstract:Recent studies show that focal brain injury, cerebral ischaemia, hypoglycaemia and seizures increase the expression of c-fos and brain-derived neurotrophic factor in brain. Here we report that hippocampal focal brain injury transiently induces the Immediate Early Genes c-fos, jun-B, c-jun and krox-24 (zif-268) messenger RNA and protein and brain-derived neurotrophic factor messenger RNA in rat dentate gyrus neurons, an effect that was blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Prior administration of the protein synthesis inhibitor cycloheximide super-induced Immediate Early Gene messenger RNA, abolished Immediate Early Gene protein induction, but had no effect on injury-mediated induction of brain-derived neurotrophic factor messenger RNA. Thus, while N-methyl-D-aspartate receptor activation results in the induction of both Immediate Early Genes and brain-derived neurotrophic factor messenger RNA, de novo synthesis of Immediate Early Gene proteins is not critical for the increased expression of brain-derived neurotrophic factor messenger RNA seen in brain after focal injury. These results suggest that brain-derived neurotrophic factor is induced after injury as an Immediate Early Gene.
Sabrina Davis - One of the best experts on this subject based on the ideXlab platform.
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A Requirement for the Immediate Early Gene zif268 in Reconsolidation of Recognition Memory after Retrieval
Neuron, 2003Co-Authors: Bruno Bozon, Sabrina Davis, Serge LarocheAbstract:Recent research has revived interest in the possibility that previously consolidated memories need to reconsolidate when recalled to return to accessible long-term memory. Evidence suggests that both consolidation and reconsolidation of certain types of memory require protein synthesis, but whether similar molecular mechanisms are involved remains unclear. Here, we explore whether zif268, an activity-dependent inducible Immediate Early Gene (IEG) required for consolidation of new memories, is also recruited for reconsolidation of recognition memory following reactivation. We show that when a consolidated memory for objects is recalled, zif268 mutant mice are impaired in further long-term but not short-term recognition memory. The impairment is specific to reactivation with the previously memorized objects in the relevant context, occurs in delayed recall, and does not recover over several days. These findings indicate that IEG-mediated transcriptional regulation in neurons is one common molecular mechanism for the storage of newly formed and reactivated recognition memories.
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Subfield-specific Immediate Early Gene expression associated with hippocampal long-term potentiation in vivo.
Supplement ... to the European journal of neuroscience., 2001Co-Authors: Pim J French, Sabrina Davis, Vincent O'connor, M Jones, Michael L. Errington, V Voss, T Truchet, C Wotjak, S Stean, Valérie DoyèreAbstract:It is not known whether NMDA receptor-dependent long-term potentiation (LTP) is mediated by similar molecular mechanisms in different hippocampal areas. To address this question we have investigated changes in Immediate Early Gene and protein expression in two hippocampal subfields following the induction of LTP in vivo and in vitro. In granule cells of the dentate gyrus, LTP induced in vivo by tetanic stimulation of the perforant path was followed by strong induction of the Immediate Early Genes (IEGs) Zif268, Arc and Homer. The increase in Zif268 mRNA was accompanied by an increase in protein expression. In contrast, we were unable to detect modulation of the IEGs Zif268, Arc, Homer and HB-GAM following induction of LTP by high-frequency stimulation of the commissural projection to CA1 pyramidal cells in vivo. In this pathway, we also failed to detect modulation of Zif268 protein levels. Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock-induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli. When LTP was induced in vitro neither CA1 pyramidal cells nor granule cells showed an increase in Zif268, Arc or Homer mRNA. However, in the slice preparation, granule cells have a different transcriptional state as basal IEG levels are elevated. These results establish the existence of subfield-specific transcriptional responses to LTP-inducing stimulation in the hippocampus of the intact animal, and demonstrate that in area CA1-enhanced transcription of Zif268, Arc and Homer is not required for the induction of late LTP.
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a requirement for the Immediate Early Gene zif268 in the expression of late ltp and long term memories
Nature Neuroscience, 2001Co-Authors: Matthew W Jones, Bruno Bozon, Serge Laroche, M L Errington, Pim J French, A Fine, T V P Bliss, Sonia Garel, Patrick Charnay, Sabrina DavisAbstract:The induction of long-term potentiation (LTP) in the dentate gyrus of the hippocampus is associated with a rapid and robust transcription of the Immediate Early Gene Zif268. We used a mutant mouse with a targeted disruption of Zif268 to ask whether this Gene, which encodes a zinc finger transcription factor, is required for the maintenance of late LTP and for the expression of long-term memory. We show that whereas mutant mice exhibit Early LTP in the dentate gyrus, late LTP is absent when measured 24 and 48 hours after tetanus in the freely moving animal. In both spatial and non-spatial learning tasks, short-term memory remained intact, whereas performance was impaired in tests requiring long-term memory. Thus, Zif268 is essential for the transition from short- to long-term synaptic plasticity and for the expression of long-term memories.
Serge Laroche - One of the best experts on this subject based on the ideXlab platform.
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A Requirement for the Immediate Early Gene zif268 in Reconsolidation of Recognition Memory after Retrieval
Neuron, 2003Co-Authors: Bruno Bozon, Sabrina Davis, Serge LarocheAbstract:Recent research has revived interest in the possibility that previously consolidated memories need to reconsolidate when recalled to return to accessible long-term memory. Evidence suggests that both consolidation and reconsolidation of certain types of memory require protein synthesis, but whether similar molecular mechanisms are involved remains unclear. Here, we explore whether zif268, an activity-dependent inducible Immediate Early Gene (IEG) required for consolidation of new memories, is also recruited for reconsolidation of recognition memory following reactivation. We show that when a consolidated memory for objects is recalled, zif268 mutant mice are impaired in further long-term but not short-term recognition memory. The impairment is specific to reactivation with the previously memorized objects in the relevant context, occurs in delayed recall, and does not recover over several days. These findings indicate that IEG-mediated transcriptional regulation in neurons is one common molecular mechanism for the storage of newly formed and reactivated recognition memories.
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a requirement for the Immediate Early Gene zif268 in the expression of late ltp and long term memories
Nature Neuroscience, 2001Co-Authors: Matthew W Jones, Bruno Bozon, Serge Laroche, M L Errington, Pim J French, A Fine, T V P Bliss, Sonia Garel, Patrick Charnay, Sabrina DavisAbstract:The induction of long-term potentiation (LTP) in the dentate gyrus of the hippocampus is associated with a rapid and robust transcription of the Immediate Early Gene Zif268. We used a mutant mouse with a targeted disruption of Zif268 to ask whether this Gene, which encodes a zinc finger transcription factor, is required for the maintenance of late LTP and for the expression of long-term memory. We show that whereas mutant mice exhibit Early LTP in the dentate gyrus, late LTP is absent when measured 24 and 48 hours after tetanus in the freely moving animal. In both spatial and non-spatial learning tasks, short-term memory remained intact, whereas performance was impaired in tests requiring long-term memory. Thus, Zif268 is essential for the transition from short- to long-term synaptic plasticity and for the expression of long-term memories.
Charles R. Gerfen - One of the best experts on this subject based on the ideXlab platform.
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Enkephalin regulates acute D2 dopamine receptor antagonist-induced Immediate-Early Gene expression in striatal neurons.
Neuroscience, 1999Co-Authors: Heinz Steiner, Charles R. GerfenAbstract:Projection neurons of the striatum release opioid peptides in addition to GABA. Our previous studies showed that the opioid peptide dynorphin regulates that subtype of projection neurons which sends axons to the substantia nigra/entopeduncular nucleus, as indicated by an inhibitory action of dynorphin/agonists on D1 dopamine receptor-mediated Immediate-Early Gene induction in these neurons. The other subtype of striatal projection neurons projects to the globus pallidus and contains the opioid peptide enkephalin. Here, we investigated whether enkephalin regulates the function of striatopallidal neurons, by analysing opioid effects on Immediate-Early Gene induction by D2 dopamine receptor blockade that occurs in these neurons. Thus, the effects of systemic and intrastriatal administration of various opioid receptor agonists and antagonists on Immediate-Early Gene expression (c-fos, zif 268) induced by the D2 receptor antagonist eticlopride were examined with in situ hybridization histochemistry. Intrastriatal infusion of enkephalin (delta and mu), but not dynorphin (kappa), receptor agonists suppressed Immediate-Early Gene induction by eticlopride in a dose-dependent manner. This suppression was blocked by the opioid receptor antagonist naloxone, confirming the involvement of opioid receptors. Repeated treatment with D2 receptor antagonists produces increased enkephalin expression and diminished Immediate-Early Gene inducibility in striatopallidal neurons, as well as behavioral effects that are attenuated compared to those of acute treatment (e.g., reduced akinesia). Naloxone reversed such behavioral recovery (i.e. reinstated akinesia), but did not significantly affect suppressed Immediate-Early Gene induction. Our results indicate that enkephalin acts, via mu and delta receptors in the striatum, to inhibit acute effects of D2 receptor blockade in striatopallidal neurons. Moreover, the present findings suggest that increased enkephalin expression after repeated D2 receptor antagonist treatment is an adaptive response that counteracts functional consequences of D2 receptor blockade, but is not involved in suppressed Immediate-Early Gene induction. Together with our earlier findings of the role of dynorphin, these results indicate that opioid peptides in the striatum serve as negative feedback systems to regulate the striatal output pathways in which they are expressed.
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d1 dopamine receptor deficient mouse cocaine induced regulation of Immediate Early Gene and substance p expression in the striatum
Neuroscience, 1996Co-Authors: John Drago, Charles R. Gerfen, H Westphal, Heinz SteinerAbstract:Psychomotor stimulants such as cocaine alter Gene expression in neurons of the striatum. Whereas many of these effects are mediated by D1 dopamine receptors, the involvement of other dopamine receptor subtypes or neurotransmitters is likely. To distinguish between these possibilities, regulation by cocaine of Immediate-Early Genes and Genes encoding neuropeptides was analysed in mice that lack functional D1 receptors. Gene expression was examined with in situ hybridization histochemistry. In these animals, cocaine failed to induce the Immediate-Early Genes c-fos and zif 268. In contrast, substance P expression was abnormally increased by this drug. These results demonstrate that some of the effects of cocaine on Gene regulation are mediated via D1 receptor-dependent mechanisms, as evidenced by the absence of Immediate-Early Gene induction in D1-deficient mice, whereas others also involve additional, non-D1 receptor mechanisms, as shown for substance P expression.
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d1 d2 dopamine receptor synergy in striatum effects of intrastriatal infusions of dopamine agonists and antagonists on Immediate Early Gene expression
Neuroscience, 1995Co-Authors: Kristen A. Keefe, Charles R. GerfenAbstract:Manipulations of D1- or D2-dopamine receptors have differential and selective effects on the striatonigral and striatopallidal output pathways of the striatum, respectively. However, combined stimulation of these receptors produces synergistic responses. To examine the locus of this interactionin vivo, we infused D1- or D2-receptor agents into the striatum of freely moving, dopamine-depleted rats given systemic injections of the D1 agonist SKF 38393 and the D2 agonist quinpirole. Expression of the Immediate Early Geneszif 268 and c-fos, as determined byin situ hybridization histochemistry, was used as a measure of changes in the function of striatal neurons. Systemic administration of SKF 38393 produced a dose-dependent increase in the expression of Immediate Early Genes in the dopamine-depleted striatum. Quinpirole, on the other hand, decreased the basal expression ofzif 268 in both the lesioned and intact striatum. However, combined administration of quinpirole with SKF 38393 significantly enhanced Immediate Early Gene expression in the dopamine-depleted striatum relative to that seen with SKF 38393 alone. Intrastriatal infusion of SKF 38393 produced a concentration-dependent increase in Immediate Early Gene expression in the striatum. Furthermore, intrastriatal application of the D1-receptor antagonist SCH 23390 blocked the induction of Immediate Early Genes by SKF 38393 given systemically either alone or with quinpirole. The induction of Immediate Early Genes by co-administration of SKF 38393 and quinpirole was also significantly attenuated by intrastriatal administration of the D2-receptor antagonist eticlopride. These data show that D1–D2 synergy is operative in the dopamine-depleted striatum, is reflected in increases in the expression of the Immediate Early Geneszif 268 and c-fos, and is a consequence of activation of both D1 and D2 receptors within the striatum rather than in extrastriatal sites. The data further suggest that the enhanced induction of Immediate Early Genes in the dopamine-depleted striatum of rats receiving SKF 38393 with quinpirole reflects a D2-mediated potentiation of a D1-dependent process.
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Tactile Sensory Input Regulates Basal and Apomorphine-Induced Immediate-Early Gene Expression in Rat Barrel Cortex
The Journal of comparative neurology, 1994Co-Authors: Heinz Steiner, Charles R. GerfenAbstract:Clipping of mystacial vibrissae on one side of the rat’s snout results in sensorimotor asymmetries in normal behavior and in behavior induced by the dopamine receptor agonist, apomorphine. Immediate-Early Gene expression, a marker for short-term changes in neuron function, was used to examine whether this sensory deprivation leads to functional changes in the somatosensory barrel cortex under experimental conditions which reveal behavioral asymmetries. The expression of c-fos and zif 268 Immediate-Early Genes was assessed with in situ hybridization histochemistry. Four hours after unilateral clipping of the mystacial vibrissae, the level of zif 268 mRNA was reduced in the corresponding part of the contralateral barrel field. Injection of apomorphine (5 mg/kg) resulted in increased expression of both c-fos and zif 268 Immediate-Early Genes in cortex and striatum. This apomorphine-induced increase was blocked in the sensory-deprived somatosensory cortex. Laminar analysis of Gene regulation showed that vibrissae removal affected Immediate-Early Gene expression in all layers of the barrel cortex. These results demonstrate that: (1) basal zif 268 Gene expression in neurons of the somatosensory cortex is dependent on sensory input, (2) cortical Immediate-Early Gene expression is increased after dopamine receptor activation, and (3) in the barrel cortex, this increase is also dependent on sensory input. We suggest that the observed reduction in Gene expression after vibrissae removal reflects decreased activation of neurons in the barrel column by removal of sensory input. o 1994 Witey-Liss, Inc.*
Paul F. Worley - One of the best experts on this subject based on the ideXlab platform.
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obligatory role for the Immediate Early Gene narp in critical period plasticity
Neuron, 2013Co-Authors: Shiyong Huang, Paul F. Worley, Michael C Chang, Alfredo Kirkwood, Elizabeth M QuinlanAbstract:Summary The Immediate Early Gene neuronal activity-regulated pentraxin (NARP) is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding protein that is specifically enriched at excitatory synapses onto fast-spiking parvalbumin-positive interneurons (FS [PV] INs). Here, we show that transgenic deletion of NARP decreases the number of excitatory synaptic inputs onto FS (PV) INs and reduces net excitatory synaptic drive onto FS (PV) INs. Accordingly, the visual cortex of NARP −/− mice is hyperexcitable and unable to express ocular dominance plasticity, although many aspects of visual function are unimpaired. Importantly, the number and strength of inhibitory synaptic contacts from FS (PV) INs onto principle neurons in the visual cortex is normal in NARP −/− mice, and enhancement of this output recovers the expression of experience-dependent synaptic plasticity. Thus the recruitment of inhibition from FS (PV) INs plays a central role in enabling the critical period for ocular dominance plasticity.
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increased expression of the Immediate Early Gene arc arg3 1 reduces ampa receptor mediated synaptic transmission
Neuron, 2006Co-Authors: Emiliano Rial M Verde, Paul F. Worley, Jane Leeosbourne, Roberto Malinow, Hollis T ClineAbstract:Arc/Arg3.1 is an Immediate-Early Gene whose expression levels are increased by strong synaptic activation, including synapse-strengthening activity patterns. Arc/Arg3.1 mRNA is transported to activated dendritic regions, conferring the distribution of Arc/Arg3.1 protein both temporal correlation with the inducing stimulus and spatial specificity. Here, we investigate the effect of increased Arc/Arg3.1 levels on synaptic transmission. Surprisingly, Arc/Arg3.1 reduces the amplitude of synaptic currents mediated by AMPA-type glutamate receptors (AMPARs). This effect is prevented by RNAi knockdown of Arc/Arg3.1, by deleting a region of Arc/Arg3.1 known to interact with endophilin 3 or by blocking clathrin-coated endocytosis of AMPARs. In the hippocampal slice, Arc/Arg3.1 results in removal of AMPARs composed of GluR2 and GluR3 subunits (GluR2/3). Finally, Arc/Arg3.1 expression occludes NMDAR-dependent long-term depression. Our results demonstrate that Arc/Arg3.1 reduces the number of GluR2/3 receptors leading to a decrease in AMPAR-mediated synaptic currents, consistent with a role in the homeostatic regulation of synaptic strength.
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Mapping behaviorally relevant neural circuits with Immediate-Early Gene expression
Current opinion in neurobiology, 2005Co-Authors: John F. Guzowski, Jerilyn A. Timlin, B. Roysam, Bruce L. Mcnaughton, Paul F. Worley, Carol A. BarnesAbstract:Immediate-Early Genes have gained widespread popularity as activity markers for mapping neuronal circuits involved in specific behaviors in many different species. In situ Immediate Early Gene detection methods provide cellular level resolution, a major benefit for mapping neuronal networks. Recent advances using fluorescence in situ hybridization also afford temporal resolution, enabling within-animal activity maps for two distinct behaviors. Moreover, use of transgenic mice with fluorescent reporter proteins driven by Immediate Early Gene promoters is enabling repeated measurements, over long time scales, of cortical activity within the same animal. These methodological innovations, coupled with recent advances in fluorescence imaging and probe development, will enable large scale mapping of behaviorally relevant circuits with temporal and three-dimensional spatial resolution in experimental animals.
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synaptic activity induced conversion of intronic to exonic sequence in homer 1 Immediate Early Gene expression
The Journal of Neuroscience, 2002Co-Authors: Daniele Bottai, John F. Guzowski, Paul F. Worley, Martin K Schwarz, Shin H Kang, Bo Xiao, Anthony Lanahan, Peter H SeeburgAbstract:Three Homer Genes regulate the activity of metabotropic glutamate receptors mGluR1a and mGluR5 and their coupling to releasable intracellular Ca2+ pools and ion channels. Only the Homer 1 Gene evolved bimodal expression of constitutive (Homer 1b and c) and Immediate Early Gene (IEG) products (Homer 1a and Ania 3). The IEG forms compete functionally with the constitutive Homer proteins. The complex expression of the Homer 1 Gene, unique for IEGs, focused our attention on the Gene organization. In contrast to most IEGs, which have Genes that are 10-fold activity-dependent increase in mRNA levels exclusively for the IEG forms. Moreover, fluorescent in situ hybridization documented that new primary Homer 1 transcripts are induced in neuronal nuclei within a few minutes after seizure, typical of IEGs, and that Homer 1b-specific exons are excluded from the activity-induced transcripts. Thus, at the resting state of the neurons, the entire Gene is constitutively transcribed at low levels to yield Homer 1b/c transcripts. Neuronal activity sharply increases the rate of transcription initiation, with most transcripts now ending within the central intron. These coordinate transcriptional events rapidly convert a constitutive Gene to an IEG and regulate the expression of functionally different Homer 1 proteins.
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environment specific expression of the Immediate Early Gene arc in hippocampal neuronal ensembles
Nature Neuroscience, 1999Co-Authors: John F. Guzowski, Bruce L. Mcnaughton, Carol A. Barnes, Paul F. WorleyAbstract:We used fluorescent in-situ hybridization and confocal microscopy to monitor the subcellular distribution of the Immediate-Early Gene Arc. Arc RNA appeared in discrete intranuclear foci within minutes of neuronal activation and subsequently disappeared from the nucleus and accumulated in the cytoplasm by 30 minutes. The time course of nuclear versus cytoplasmic Arc RNA accumulation was distinct, and could therefore be used to infer the activity history of individual neurons at two times. Following sequential exposure of rats to two different environments or to the same environment twice, the proportion of CA1 neurons with cytoplasmic, nuclear or overlapping Arc expression profiles matched predictions derived from ensemble neurophysiological recordings of hippocampal neuronal ensembles. Arc Gene induction is thus specifically linked to neural encoding processes.
