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Selective survival and maturation of adult-born dentate granule cells expressing the immediate early gene Arc/Arg3.1.

Kuipers SD, Tiron A, Soule J, Messaoudi E, Trentani A, Bramham CR - PLoS ONE (2009)

Bottom Line: Contrary to expectation, LTP did not induce Arc expression in newborn cells at any age, suggesting they might be refractory to synaptically-evoked Arc expression for at least one month.Importantly, however, spontaneous expression of Arc was detected in BrdU-labeled cells and strongly associated with the survival and maturation of NeuN-positive DGCs.These results suggest an unexpected early role for Arc in adult-born DGCs, distinct from its functions in LTP, LTD, and homeostatic synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Bergen, Norway.

ABSTRACT
Progenitor cells in the adult dentate gyrus provide a constant supply of neuronal precursors, yet only a small fraction of these cells survive and develop into mature dentate granule cells (DGCs). A major challenge of current research is thus to understand the stringent selection process that governs the maturation and functional integration of adult-born DGCs. In mature DGCs, high-frequency stimulation (HFS) of the perforant path input elicits robust expression of the immediate early gene Arc/Arg3.1, trafficking of its mRNA to dendrites, and local synthesis of the protein necessary for consolidation of long-term potentiation (LTP). Given the synaptic commitment inherent in LTP consolidation, we considered that HFS-evoked expression of Arc could be used to timemap the functional integration of newborn DGCs. Dividing cells were birthmarked by BrdU-labeling at 1, 7, 14, 21, or 28 days prior to induction of LTP and expression of Arc was examined by confocal microscopy. Contrary to expectation, LTP did not induce Arc expression in newborn cells at any age, suggesting they might be refractory to synaptically-evoked Arc expression for at least one month. Importantly, however, spontaneous expression of Arc was detected in BrdU-labeled cells and strongly associated with the survival and maturation of NeuN-positive DGCs. Moreover, Arc expression at the earliest ages (1 and 7 days), clearly precedes the formation of glutamatergic synapses on new neurons. These results suggest an unexpected early role for Arc in adult-born DGCs, distinct from its functions in LTP, LTD, and homeostatic synaptic plasticity.

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Stable LTP in BrdU-injected rats.a, Time course plot illustrates changes in the medial perforant path-evoked fEPSP slope expressed in percentage of baseline. Values are means±SEM. HFS is indicated by the arrow. Average field potential traces (10 sweeps) collected at the end of baseline (Baseline) and at the end of recording (Post-HFS) are shown below. Calibration: 5 mV, 2 ms. b, Magnitude of fEPSP slope changes was equal across all groups. n = 8 per group.
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pone-0004885-g002: Stable LTP in BrdU-injected rats.a, Time course plot illustrates changes in the medial perforant path-evoked fEPSP slope expressed in percentage of baseline. Values are means±SEM. HFS is indicated by the arrow. Average field potential traces (10 sweeps) collected at the end of baseline (Baseline) and at the end of recording (Post-HFS) are shown below. Calibration: 5 mV, 2 ms. b, Magnitude of fEPSP slope changes was equal across all groups. n = 8 per group.

Mentions: LTP was induced in the DG, using methodology previously described [25], [26]. Rats were anesthetized with urethane (1.5 g/kg i.p.) and placed in a stereotaxic apparatus. Rectal temperature was maintained at 36.5°C using a servo-heating pad. Electrodes were placed for selective unilateral stimulation of the medial perforant path and recording of evoked field potentials from the dentate gyrus. Stereotaxic coordinates relative to Bregma were 3.9 mm posterior, 2.3 mm lateral for recording and 7.9 mm posterior, 4.2 mm lateral for stimulation. A bipolar stimulating electrode was placed into the dorsomedial angular bundle for stimulating the medial perforant path. After making a slit in the dura, a Teflon-coated stainless steel wire recording electrode was slowly lowered into the dorsal hippocampus until positive field excitatory postsynaptic potential (fEPSP) of maximum slope was obtained in the dentate hilus. Biphasic rectangular pulses of 150 µs duration were applied every 30 sec throughout the experiment, using an intensity set to elicit a population spike amplitude of 30% of the maximal response. After 20 minutes of stable baseline recording, LTP was induced using a 400 Hz protocol that consisted of eight pulses, repeated four times, at 10 sec intervals. Three sessions of HFS were given at intervals of 5 minutes. Signals from the dentate hilus were amplified, filtered (1 Hz to 10 kHz), and digitized (25 kHz). Acquisition and analysis of field potentials was accomplished using DataWave Technologies (Longmont, CO) WorkBench software. Responses were normalized to baseline and statistics were based on values obtained during the last 5 minutes of recording (Fig. 2a,b). All animals included in the study exhibited stable fEPSP slope increases of at least 25% at the end of LTP recording.


Selective survival and maturation of adult-born dentate granule cells expressing the immediate early gene Arc/Arg3.1.

Kuipers SD, Tiron A, Soule J, Messaoudi E, Trentani A, Bramham CR - PLoS ONE (2009)

Stable LTP in BrdU-injected rats.a, Time course plot illustrates changes in the medial perforant path-evoked fEPSP slope expressed in percentage of baseline. Values are means±SEM. HFS is indicated by the arrow. Average field potential traces (10 sweeps) collected at the end of baseline (Baseline) and at the end of recording (Post-HFS) are shown below. Calibration: 5 mV, 2 ms. b, Magnitude of fEPSP slope changes was equal across all groups. n = 8 per group.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654102&req=5

pone-0004885-g002: Stable LTP in BrdU-injected rats.a, Time course plot illustrates changes in the medial perforant path-evoked fEPSP slope expressed in percentage of baseline. Values are means±SEM. HFS is indicated by the arrow. Average field potential traces (10 sweeps) collected at the end of baseline (Baseline) and at the end of recording (Post-HFS) are shown below. Calibration: 5 mV, 2 ms. b, Magnitude of fEPSP slope changes was equal across all groups. n = 8 per group.
Mentions: LTP was induced in the DG, using methodology previously described [25], [26]. Rats were anesthetized with urethane (1.5 g/kg i.p.) and placed in a stereotaxic apparatus. Rectal temperature was maintained at 36.5°C using a servo-heating pad. Electrodes were placed for selective unilateral stimulation of the medial perforant path and recording of evoked field potentials from the dentate gyrus. Stereotaxic coordinates relative to Bregma were 3.9 mm posterior, 2.3 mm lateral for recording and 7.9 mm posterior, 4.2 mm lateral for stimulation. A bipolar stimulating electrode was placed into the dorsomedial angular bundle for stimulating the medial perforant path. After making a slit in the dura, a Teflon-coated stainless steel wire recording electrode was slowly lowered into the dorsal hippocampus until positive field excitatory postsynaptic potential (fEPSP) of maximum slope was obtained in the dentate hilus. Biphasic rectangular pulses of 150 µs duration were applied every 30 sec throughout the experiment, using an intensity set to elicit a population spike amplitude of 30% of the maximal response. After 20 minutes of stable baseline recording, LTP was induced using a 400 Hz protocol that consisted of eight pulses, repeated four times, at 10 sec intervals. Three sessions of HFS were given at intervals of 5 minutes. Signals from the dentate hilus were amplified, filtered (1 Hz to 10 kHz), and digitized (25 kHz). Acquisition and analysis of field potentials was accomplished using DataWave Technologies (Longmont, CO) WorkBench software. Responses were normalized to baseline and statistics were based on values obtained during the last 5 minutes of recording (Fig. 2a,b). All animals included in the study exhibited stable fEPSP slope increases of at least 25% at the end of LTP recording.

Bottom Line: Contrary to expectation, LTP did not induce Arc expression in newborn cells at any age, suggesting they might be refractory to synaptically-evoked Arc expression for at least one month.Importantly, however, spontaneous expression of Arc was detected in BrdU-labeled cells and strongly associated with the survival and maturation of NeuN-positive DGCs.These results suggest an unexpected early role for Arc in adult-born DGCs, distinct from its functions in LTP, LTD, and homeostatic synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Bergen, Norway.

ABSTRACT
Progenitor cells in the adult dentate gyrus provide a constant supply of neuronal precursors, yet only a small fraction of these cells survive and develop into mature dentate granule cells (DGCs). A major challenge of current research is thus to understand the stringent selection process that governs the maturation and functional integration of adult-born DGCs. In mature DGCs, high-frequency stimulation (HFS) of the perforant path input elicits robust expression of the immediate early gene Arc/Arg3.1, trafficking of its mRNA to dendrites, and local synthesis of the protein necessary for consolidation of long-term potentiation (LTP). Given the synaptic commitment inherent in LTP consolidation, we considered that HFS-evoked expression of Arc could be used to timemap the functional integration of newborn DGCs. Dividing cells were birthmarked by BrdU-labeling at 1, 7, 14, 21, or 28 days prior to induction of LTP and expression of Arc was examined by confocal microscopy. Contrary to expectation, LTP did not induce Arc expression in newborn cells at any age, suggesting they might be refractory to synaptically-evoked Arc expression for at least one month. Importantly, however, spontaneous expression of Arc was detected in BrdU-labeled cells and strongly associated with the survival and maturation of NeuN-positive DGCs. Moreover, Arc expression at the earliest ages (1 and 7 days), clearly precedes the formation of glutamatergic synapses on new neurons. These results suggest an unexpected early role for Arc in adult-born DGCs, distinct from its functions in LTP, LTD, and homeostatic synaptic plasticity.

Show MeSH