A Transgenic Marker for Newly Born Granule Cells in Dentate Gyrus

Overstreet, Linda S.; Hentges, Shane T.; Bumaschny, Viviana Florencia; Souza, Flávio Silva Junqueira de; Smart, James L.; Santangelo, Andrea Mariana; Low, Malcolm J.; Westbrook, Gary L.; Rubinstein, Marcelo

doi:10.1523/jneurosci.5173-03.2004

Cited by 190 publications

(266 citation statements)

References 52 publications

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“…1 A-C), with only very few EGFP cells in the hilus or molecular layer. These cells displayed immature neuronal morphology, with short dendrites that projected through the granule cell layer but not the molecular layer, consistent with previous reports (Overstreet et al, 2004;.…”

Section: Resultssupporting

confidence: 92%

“…We examined the brains of 11 wild-type and six LIS1 mutant mice in a series of immunohistochemical studies. Mature granule cells were identified using an antibody for NeuN or PROX1, which is expressed in granule cell nuclei (Liu et al, 2000;Pleasure et al, 2000;Elliott et al, 2001;Szabadics et al, 2010) but absent or barely detectable in POMC:EGFP-labeled neurons (Overstreet et al, 2004;. As expected, granule cells formed a discrete, compact cell layer in wild-type control mice ( Fig.…”

Section: Resultsmentioning

confidence: 53%

“…To examine the effect of reduced LIS1 on excitability in a malformed DG, we crossed LIS1 ϩ/Ϫ mutants with POMC:EGFP transgenic reporter mice. In these animals, EGFP is expressed in a subset of adult-generated granule cells (ϳ1-3 weeks postmitotic) (Cowley et al, 2001;Overstreet et al, 2004;. We examined the brains of 11 wild-type and six LIS1 mutant mice in a series of immunohistochemical studies.…”

Section: Resultsmentioning

confidence: 99%

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LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

et al. 2012

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Type I lissencephaly, a neuronal migration disorder characterized by cognitive disability and refractory epilepsy, is often caused by heterozygous mutations in the LIS1 gene. Histopathologies of malformation-associated epilepsies have been well described, but it remains unclear whether hyperexcitability is attributable to disruptions in neuronal organization or abnormal circuit function. Here, we examined the effect of LIS1 deficiency on excitatory synaptic function in the dentate gyrus of hippocampus, a region believed to serve critical roles in seizure generation and learning and memory. Mice with heterozygous deletion of LIS1 exhibited robust granule cell layer dispersion, and adult-born granule cells labeled with enhanced green fluorescent protein were abnormally positioned in the molecular layer, hilus, and granule cell layer. In whole-cell patch-clamp recordings, reduced LIS1 function was associated with greater excitatory synaptic input to mature granule cells that was consistent with enhanced release probability at glutamatergic synapses. Adult-born granule cells that were ectopically positioned in the molecular layer displayed a more rapid functional maturation and integration into the synaptic network compared with newborn granule cells located in the hilus or granule cell layer or in wild-type controls. In a conditional knock-out mouse, induced LIS1 deficiency in adulthood also enhanced the excitatory input to granule cells in the absence of neuronal disorganization. These findings indicate that disruption of LIS1 has direct effects on excitatory synaptic transmission independent of laminar disorganization, and the ectopic position of adult-born granule cells within a malformed dentate gyrus critically influences their functional maturation and integration.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

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LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

et al. 2012

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“…Recent progress in generating transgenic mouse lines facilitated the labeling and analysis of adult neural stem cells and newborn neurons. However, in traditional transgenic lines [19], reporter genes driven by transient marker gene promoters are only expressed temporally in immature stage, thus making genetic manipulation and long-tem tracing of newborn neurons difficult. Transgenic mice expressing inducible recombinase (CreER T2 ) [20] in neuronal stem or precursor cells provide new approaches to neurogenesis labeling and manipulation [10,21].…”

Section: Introductionmentioning

confidence: 99%

Pulse labeling and long-term tracing of newborn neurons in the adult subgranular zone

Cheng

Huang

et al. 2010

Cell Res

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Research over the past decades has demonstrated that adult brain produces neural progenitor cells which proliferate and differentiate to newborn neurons that integrate into the existing circuit. However, detailed differentiation processes and underlying mechanisms of newly generated neurons are largely unknown due to the limitation of available methods for labeling and manipulating neural progenitor cells and newborn neurons. In this study, we designed a tightly controlled, noninvasive system based on Cre/loxP recombination to achieve long-term tracing and genetic manipulation of adult neurons in vivo. In this system, tamoxifen-inducible recombinase, CreER T2 , was driven by BAC-based promoter of doublecortin (DCX, a marker of newborn neurons). By crossing this Cre line with reporter mouse, we found that newborn neurons in the dentate gyrus (DG) could be selectively pulse-labeled by tamoxifeninduced expression of yellow fluorescent protein (YFP). YFP-positive neurons were identified by coimmunostaining with cell type-specific markers and characterized by electrophysiological recording. Furthermore, analysis of the migration of these neurons showed that the majority of these labeled neurons migrated to the inner part of granule cell layer. Moreover, spine growth of inner molecular layer of newborn granule neurons takes a dynamic pattern of invert U-shape, in contrast to the wedge-shaped change in the outer molecular layer. Our transgenic tool provides an efficient way to selectively label and manipulate newborn neuron in adult mouse DG.

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“…The dentate gyrus of the hippocampus is one of the few adult brain regions where proliferating cells differentiate into young neurons [1,2], which integrate anatomically and physiologically into the hippocampal neuronal network [3][4][5][6]. Changes in the extent of adult hippocampal neurogenesis are associated with changes in the performance of animals in hippocampus-dependent behavioral tasks [7][8][9][10][11], and a recent study of conditional TLX knockout mice, a gene expressed by adult neural stem cells, suggest a causal link between the performance in specific aspects of behavioral tasks and neurogenesis [12].…”

Section: Introductionmentioning

confidence: 99%

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

Klaus

Hauser

Slomianka

et al. 2009

Behavioural Brain Research

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A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice Klaus, F; Hauser, T; Slomianka, L; Amrein, I; Lipp, H P Klaus, F; Hauser, T; Slomianka, L; Amrein, I; Lipp, H P (2009). A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice. A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice Abstract Exercise is one of the best-known stimulators of adult hippocampal neurogenesis, but it is not known if voluntary changes in the intensity of exercise are accompanied by changes in neurogenesis. In this study we investigated whether a reward influences the performance in a running wheel and the rate of cell proliferation, neuronal differentiation and cell death in C57BL/6 mice. Mice had free access to a running wheel during the first week of the experiment. In the second week, animals were rewarded for their performance and compared to normal voluntary running and control mice. A reward significantly increased the performance by 78% when compared to the non-rewarded performance of the first week.The performance of the non-rewarded runners remained relatively constant. Fourteen days of exercise significantly increased cell proliferation by 27% and the number of doublecortin immunoreactive cells by 46%. A reward and the associated increase of performance did not modulate proliferation, cell death or the number of cells entering the neuronal lineage. We suggest that, in C57BL/6 mice, either exercise increases adult hippocampal neurogenesis to a ceiling value, which is reached by a performance at or below the level achieved by voluntary wheel running, or that a possible positive effect of increased running-wheel activity is balanced by stress resulting from rewarded running, which is no longer performed on a strictly voluntary basis. We suggest that, in C57BL/6 mice, either exercise increases adult hippocampal neurogenesis to a ceiling value, which is reached by a performance at or below the level achieved by voluntary wheel running, or that a possible positive effect of increased is balanced by stress resulting from rewarded running, which is no longer performed on a strictly voluntary basis.

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A Transgenic Marker for Newly Born Granule Cells in Dentate Gyrus

Cited by 190 publications

References 52 publications

LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

Pulse labeling and long-term tracing of newborn neurons in the adult subgranular zone

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

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