Molecular heterogeneity along the dorsal–ventral axis of the murine hippocampal CA1 field: a microarray analysis of gene expression

doi:10.1016/j.neuroscience.2005.08.082

Neuroscience

Volume 137, Issue 1, 2006, Pages 177-186

https://doi.org/10.1016/j.neuroscience.2005.08.082 Get rights and content

Abstract

There has been increasing interest in functional heterogeneity along the septotemporal, dorsal–ventral (D–V) axis of the hippocampus. Although anatomical connectivity and lesion studies point to discrete roles for these sub-regions, the contribution of differential gene expression across this axis has not been systematically studied. Here we present findings from an Affymetrix microarray screen aimed at identifying genes in the CA1 region of the adult murine hippocampus that show significant differential expression along the D–V axis. Our results indicate that the vast majority of monitored genes (>90%) had tissue expression levels that differed by less than 20% between regions, while less than 0.1% of genes had expression levels that varied more than three-fold by sub-region. Only 23 probes showed a CA1 dorsoventral signal intensity ratio greater than three: 18 enriched dorsally and five enriched ventrally. Probes with the greatest difference in expression levels represent a range of genes with known functions in patterning and signaling, as well as genes without known function. Selective screening with digoxigenin-labeled in situ hybridization confirms the existence of CA1 sub-regionalized expression, with some genes exhibiting a graded expression pattern across the D–V axis, and others restricted to a discrete region. Our findings demonstrate that there are gene expression differences across the D–V axis of the adult murine hippocampus within traditionally recognized cytoarchitecturally defined boundaries. Combined with the previously recognized differences in connectivity and results from lesion studies, our data further confirm the existence of functional heterogeneity along the D–V axis.

Section snippets

Animals and tissue

All procedures were approved by the Institutional Animal Care and Use Committee, and conform to the National Institutes of Health guidelines on the ethical use of animals. Eight-to-10-week-old 129SVEV male mice were obtained from Taconic (Germantown, NY, USA). For micro-dissection and DNA microarray analysis, brains were extracted and immediately placed on ice. Extracted brains were sliced coronally on a Series 1000 Vibratome (Intracel, Shepreth, UK) in 400μm-thick sections and placed in RNA

Array data

Our aim was to identify genes that were differentially expressed along the dorsoventral axis of the CA1 region of the hippocampus enriched in the hippocampus relative to underlying cortex. An overview of the data reveals that of the 22,626 probes on the array, 6764 (29.9%) were “absent” (i.e. did not have expression above background levels). A number of genes showed enrichment in the cortical samples over the CA1 regions, with 233 genes showing greater than two-fold enrichment in the cortical

Discussion

Numerous groups have successfully used microarrays to define molecular markers of previously recognized anatomical structures, for example in sub-regions of the amygdala (Zirlinger et al., 2001) and the hippocampus (Lein et al., 2004). In general, those studies have concluded that gene expression patterns respect regional boundaries that have previously been established cytoarchitecturally. Here we present data from a screen for genes that are differentially expressed within one

Acknowledgments

We would like to thank Lauren Tanabe for initial work generating in situ probes, Vladan Miljkovic at the Columbia Microarray Project for performing array hybridizations, and Paul Pavlidis for performing RMA extraction of Affymetrix data. This work was supported by an APA/Wyeth Pharmaceuticals M.D./Ph.D. Psychiatric Research Fellowship and a NARSAD Young Investigator Award to E.D.L., grants P01 MH060970, MH068542-1 and a NARSAD Distinguished Investigator Award to R.H. and grant MH067721 to E.S.

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Citation Excerpt :
Among the implications of this large-scale functional diversification is the hypothesis that specialization also exists in the local neuronal circuitry along the hippocampus (Small et al., 2011; Strange et al., 2014; Tushev and Schuman, 2016). In fact, growing evidence indicates that there is a specialization of the intrinsic neuronal network between the two opposite hippocampal segments, namely the dorsal (DH) and the ventral (VH) hippocampi, which can be observed at all levels of neuronal organization, including molecular and gene expression profiles (Leonardo et al., 2006; Thompson et al., 2008; Dong et al., 2009; Zoladz et al., 2012; Cembrowski et al., 2016), the properties of pyramidal neurons (Kjelstrup et al., 2008; Dougherty et al., 2012, 2013; Marcelin et al., 2012; Honigsperger et al., 2015; Malik et al., 2016; Babiec et al., 2017; Malik and Johnston, 2017), the molecular composition and the function of neurotransmitter receptors (Sotiriou et al., 2005; Pandis et al., 2006; Gu et al., 2013; McEown and Treit, 2013; Kouvaros and Papatheodoropoulos, 2016a), the synaptic plasticity (Papatheodoropoulos and Kostopoulos, 2000; Maruki et al., 2001; Colgin et al., 2004; Grigoryan et al., 2012; Kenney and Manahan-Vaughan, 2013; Papatheodoropoulos, 2015; Grigoryan and Segal, 2016; Kouvaros and Papatheodoropoulos, 2016b), and the physiological neuronal oscillations (Patel et al., 2013; Long et al., 2015). The hippocampal network organizes a variety of periodic physiological activities of which the most prominent is the population activity pattern of sharp wave-ripples (SPW-Rs), (Buzsáki, 2015; Colgin, 2016).
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Molecular neuroscienceMolecular heterogeneity along the dorsal–ventral axis of the murine hippocampal CA1 field: a microarray analysis of gene expression

Abstract

Section snippets

Animals and tissue

Array data

Discussion

Acknowledgments

Neuroscience

Neurosci Biobehav Rev

Dev Biol

Biochim Biophys Acta

Cell

Prog Neurobiol

Curr Opin Neurobiol

Mol Cell Neurosci

Lamellar organization of hippocampal pathways

Exp Brain Res

Double dissociation of function within the hippocampusspatial memory and hyponeophagia

Behav Neurosci

Double dissociation of function within the hippocampusa comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions

Behav Neurosci

Perirhinal and postrhinal cortices of the ratinterconnectivity and connections with the entorhinal cortex

J Comp Neurol

Functional differentiation along the anterior–posterior axis of the hippocampus in monkeys

J Neurophysiol

Declarative memoryinsights from cognitive neurobiology

Annu Rev Psychol

Cluster analysis display of genome-wide expression patterns

Proc Natl Acad Sci U S A

The ephrins and Eph receptors in neural development

Annu Rev Neurosci

The N-terminal cysteine cluster is essential for membrane targeting of B/K protein

Biochem J

Sex genes for genomic analysis in human braininternal controls for comparison of probe level data extraction

BMC Bioinformatics

The neuropsychology of anxietyan enquiry into the functions of the septo-hippocampal system

Exploration, normalization, and summaries of high density oligonucleotide array probe level data

Biostatistics

Molecular neuroscience
Molecular heterogeneity along the dorsal–ventral axis of the murine hippocampal CA1 field: a microarray analysis of gene expression