Defining a Molecular Atlas of the Hippocampus Using DNA Microarrays and High-Throughput<i>In Situ</i>Hybridization

Lein, Ed; Zhao, Xinyu; Gage, Fred H.

doi:10.1523/jneurosci.4710-03.2004

Cited by 256 publications

(280 citation statements)

References 40 publications

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“…Specifically, the technique of high-throughput in situ hybridization has made it possible to compare the expression patterns of hundreds to thousands of genes across the subfields of the structure. These studies have shown that the pyramidal cells in CA3, CA2, and CA1 have distinct molecular identities, and while it remains difficult to make the leap from protein to computation, the data largely agrees with Cajal's original boundaries of the CA fields [48,103] (Figure I).…”

Section: Box 2: Genes In Circuitssupporting

confidence: 57%

Updating hippocampal representations: CA2 joins the circuit

Jones

McHugh

2011

Trends in Neurosciences

114

106

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The hippocampus integrates the encoding, storage and recall of memories, binding the spatiotemporal and sensory information that constitutes experience and keeping episodes in their correct context. The rapid and accurate processing of such daunting volumes of continuouslychanging data relies on dynamically assigning different aspects of mnemonic processing to specialized, interconnected networks corresponding to the anatomical subfields of dentate gyrus (DG), CA3 and CA1. However, differentially processed information ultimately has to be reintegrated into conjunctive representations, and this is unlikely to be achieved by unidirectional, sequential steps through a DG-CA3-CA1 loop. In this Review, we highlight recently discovered anatomical and physiological features that are likely to necessitate updates to the hippocampal circuit diagram, particularly by incorporating the oft-neglected CA2 region.3

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Section: Box 2: Genes In Circuitssupporting

confidence: 57%

Updating hippocampal representations: CA2 joins the circuit

Jones

McHugh

2011

Trends in Neurosciences

114

106

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“…For example, in the hippocampus it is expressed largely in the CA1 stratum pyramidale (Fig. 2C, Inset), a region containing excitatory pyramidal neurons of different physiological and molecular identities (29)(30)(31).…”

Section: Resultsmentioning

confidence: 99%

Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

Goff

Groff

Sauvageau

et al. 2015

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

159

131

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Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNAnull mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring proteincoding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.T he exquisite complexity of the mammalian brain derives from its vast diversity of neuronal and glial cell types (1, 2). The specification and differentiation of such a variety of cell types during brain development is finely orchestrated spatiotemporally by the regulation of complex transcriptional programs. Increasing evidence points to a role for long noncoding RNAs (lncRNAs) as key regulatory elements of this process. Intriguingly, within the mammalian body, the largest repertoire and diversity of lncRNA genes outside the germ line occurs in the brain (3-10), where lncRNAs exhibit regional and cell-specific localization (6, 10). Although many unanswered questions remain regarding the functional activity and molecular mechanisms of lncRNA loci, the expression patterns of lncRNAs may serve as a proxy signal for important, context-specific biological activity.A role for lncRNA genes in brain development and function is supported by the fact that ablation of two lncRNA loci, Evf2 and Pantr2 (linc-Brn1b), perturbs neuronal development (11, 12). Loss of Evf2, a developmentally regulated lncRNA that controls transcriptional activity through cooperation with the homeodomain protein DLX-2 (11), leads to abnormal development and synaptic function of hippocampal GABAergic interneurons (11). Similarly, ablation of the Pantr2 locus results in a decreased number of intermediate progenitors in the developing telencephalon, reduced neurons in L2/3 of the cerebral cortex, and disorganization of the barrel cortex (12). Furthermore, human genetic studies have pointed to lncRNAs as potential factors in brain disorders (10,(13)(14)(15)(16).To gain preliminary insights into the functional and physiological relevance of lncRNA loci in vivo, we previously generated knockout (KO) mouse models of ...

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“…Along these lines, area CA2 expresses high levels of STEP (Boulanger et al, 1995); yet, unlike the hilus, it is relatively resistant to excitotoxic cell death (Zhang et al, 1997;El Bahh et al, 1999). Mechanistically, it is not known why CA2 neurons are resistant, although numerous studies have shown that CA2 pyramidal neurons are enriched in an array of receptors and trophic factors (Tucker et al, 1993;Ochiishi et al, 1999;Lein et al, 2005) that may affect excitability and/or provide trophic support and thus decrease susceptibility to excitotoxic stimuli. Likewise, divergence also holds at the level of synaptic afferents (Haglund et al, 1984;Köhler et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase

Choi¹,

Lin²,

Lee³

et al. 2007

J. Neurosci.

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Excitotoxic cell death is one of the precipitating events in the development of temporal lobe epilepsy. Of particular prominence is the loss of GABAergic hilar neurons. Although the molecular mechanisms responsible for the selective vulnerability of these cells are not well understood, activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway has been implicated in neuroprotective responses to excitotoxicity in other neuronal populations. Here, we report that high levels of the striatalenriched protein tyrosine phosphatase (STEP), a key regulator of ERK/MAPK signaling, are found in vulnerable somatostatinimmunoreactive hilar interneurons. Under both control conditions and after pilocarpine-induced status epilepticus (SE), ERK/MAPK activation was repressed in STEP-immunoreactive hilar neurons. This contrasts with robust SE-induced ERK/MAPK activation in the granule cell layer of the dentate gyrus, a cell region that does not express STEP. During pilocarpine-induced SE, in vivo disruption of STEP activity allowed activation of the MAPK pathway, leading to immediate-early gene expression and significant rescue from cell death. Thus, STEP increases the sensitivity of neurons to SE-induced excitotoxicity by specifically blocking a latent neuroprotective response initiated by the MAPK pathway. These findings identify a key set of signaling events that render somatostatinergic hilar interneurons vulnerable to SE-induced cell death.

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Defining a Molecular Atlas of the Hippocampus Using DNA Microarrays and High-ThroughputIn SituHybridization

Cited by 256 publications

References 40 publications

Updating hippocampal representations: CA2 joins the circuit

Updating hippocampal representations: CA2 joins the circuit

Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase

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