Transcriptional profiling reveals strict boundaries between hippocampal subregions

The hippocampus consists of distinct anatomic regions that have been demonstrated to have different biological functions. To explore the molecular differences between hippocampal subregions, we performed transcriptional profiling analysis by using DNA microarray technology. The cRNA derived from the CA1, CA3, and dentate gyrus regions of the hippocampus and from spinal cord was hybridized to Affymetrix high‐density oligo arrays. This systematic approach revealed sets of genes that were expressed specifically in subregions of the hippocampus corresponding to predefined cytoarchitectural boundaries, which could be confirmed by in situ hybridization and Real Time quantitative polymerase chain reaction. The relative enrichment and absence of genes in the hippocampal subregions support the conclusion that there is a molecular basis for the previously defined anatomic subregions of the hippocampus and also reveal genes that could be important in defining the unique functions of the hippocampal subfields. J. Comp. Neurol. 441:187–196, 2001. © 2001 Wiley‐Liss, Inc.

[1]  T. Blackstad.  Commissural connections of the hippocampal region in the rat, with special reference to their mode of termination , 1956, The Journal of comparative neurology.

[2]  J. Altman,et al.  Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats , 1965, The Journal of comparative neurology.

[3]  R. Porter.  Progress in Brain Research , 1965, Nature.

[4]  J. Hinds,et al.  Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. , 1977, Science.

[5]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[6]  R. Passingham.  The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[7]  M. Segal.  A potent inhibitory monosynaptic hypothalamo-hippocampal connection , 1979, Brain Research.

[8]  W. Cowan,et al.  A study of subcortical afferents to the hippocampal formation in the rat , 1979, Neuroscience.

[9]  D. Prince,et al.  Variations in electrophysiological properties of hippocampal neurons in different subfields , 1982, Brain Research.

[10]  W. J. Brown,et al.  Temporal Lobe Volumetric Cell Densities in Temporal Lobe Epilepsy , 1984, Epilepsia.

[11]  D. Amaral,et al.  The distribution of acetylcholinesterase in the hippocampal formation of the monkey , 1984, The Journal of comparative neurology.

[12]  F. Gaarskjaer.  The organization and development of the hippocampal mossy fiber system , 1986, Brain Research Reviews.

[13]  N. Tamamaki,et al.  Three-dimensional analysis of the whole axonal arbors originating from single CA2 pyramidal neurons in the rat hippocampus with the aid of a computer graphic technique , 1988, Brain Research.

[14]  J. Darnell,et al.  Fetal and adult localization of C/EBP: evidence for combinatorial action of transcription factors in cell-specific gene expression. , 1990, Development.

[15]  D. Amaral,et al.  Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat , 1990, The Journal of comparative neurology.

[16]  K. Schlingensiepen,et al.  High basal expression of the zif 268 immediate early gene in cortical layers IV and VI, in CA1 and in the corpus striatum - an in situ hybridization study , 1991, Neuroscience Letters.

[17]  L. M. Gonzalo,et al.  Effects of alcoholization on the rat hippocampus , 1991, Neuroscience Letters.

[18]  P. Ernfors,et al.  Transient and persistent expression of NT-3/HDNF mRNA in the rat brain during postnatal development , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  M. Witter,et al.  Morphological and functional correlates of borders in the entorhinal cortex and hippocampus , 1993, Hippocampus.

[20]  C. Bondy,et al.  Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I gene expression during brain development , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  C. Cotman,et al.  Distribution of basic fibroblast growth factor in the developing rat brain , 1994, Neuroscience.

[22]  JW Polli,et al.  Expression of a calmodulin-dependent phosphodiesterase isoform (PDE1B1) correlates with brain regions having extensive dopaminergic innervation , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  F. Eckenstein,et al.  Cellular distribution, subcellular localization and possible functions of basic and acidic fibroblast growth factors. , 1994, Biochemical pharmacology.

[24]  A. Camuzat,et al.  Structure and Cellular Distribution of Mouse Brain Testican , 1996, The Journal of Biological Chemistry.

[25]  L. Wodicka,et al.  Genome-wide expression monitoring in Saccharomyces cerevisiae , 1997, Nature Biotechnology.

[26]  T. Branchek,et al.  Distribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous system. , 1997, Brain research. Molecular brain research.

[27]  F. Gage,et al.  More hippocampal neurons in adult mice living in an enriched environment , 1997, Nature.

[28]  F. Gage,et al.  Stem cells of the central nervous system. , 1998, Current opinion in neurobiology.

[29]  P. Coleman,et al.  PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease , 1998, Neuroscience.

[30]  D. Clemmons,et al.  Differential Expression and Biological Effects of Insulin-like Growth Factor-binding Protein-4 and -5 in Vascular Smooth Muscle Cells* , 1998, The Journal of Biological Chemistry.

[31]  F. Gage.  Discussion point Stem cells of the central nervous system , 1998, Current Opinion in Neurobiology.

[32]  F. Gage,et al.  Adult‐generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles , 1999, The Journal of comparative neurology.

[33]  E. Grove,et al.  Patterning events and specification signals in the developing hippocampus. , 1999, Cerebral cortex.

[34]  K. Mikoshiba,et al.  Gene expression of oligodendrocyte markers in human amniotic epithelial cells using neural cell-type-specific expression system , 1999, Neuroscience Letters.

[35]  E. Gould,et al.  Rapid extension of axons into the CA3 region by adult‐generated granule cells , 1999, The Journal of comparative neurology.

[36]  Expression of the thymosin beta10 gene in normal and kainic acid-treated rat forebrain. , 1999, Brain research. Molecular brain research.

[37]  T. Palmer,et al.  Fibroblast Growth Factor-2 Activates a Latent Neurogenic Program in Neural Stem Cells from Diverse Regions of the Adult CNS , 1999, The Journal of Neuroscience.

[38]  M. Jackson,et al.  Gene expression profiles of laser-captured adjacent neuronal subtypes , 1999, Nature Medicine.

[39]  Martin E. Schwab,et al.  Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 , 2000, Nature.

[40]  F. Gage,et al.  Regenerating the damaged central nervous system , 2000, Nature.

[41]  Edwin J. Weeber,et al.  A Role for the β Isoform of Protein Kinase C in Fear Conditioning , 2000, The Journal of Neuroscience.

[42]  E. Winzeler,et al.  Genomics, gene expression and DNA arrays , 2000, Nature.

[43]  E. Brown,et al.  Genomic analysis of gene expression in C. elegans. , 2000, Science.

[44]  L. Wodicka,et al.  Regional and strain-specific gene expression mapping in the adult mouse brain. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Sweatt,et al.  A role for the beta isoform of protein kinase C in fear conditioning. , 2000, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  C. Shatz,et al.  Dynamic regulation of BDNF and NT‐3 expression during visual system development , 2000, The Journal of comparative neurology.

[47]  P. Eriksson,et al.  Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[48]  Wei He,et al.  Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1 , 2000, Nature.

[49]  P. Horner,et al.  Adult Spinal Cord Stem Cells Generate Neurons after Transplantation in the Adult Dentate Gyrus , 2000, The Journal of Neuroscience.

[50]  I. Torres-Aleman,et al.  Circulating Insulin-Like Growth Factor I Mediates Effects of Exercise on the Brain , 2000, The Journal of Neuroscience.

[51]  David J. Lockhart,et al.  Expressing what's on your mind: DNA arrays and the brain , 2001, Nature Reviews Neuroscience.

[52]  M. Zirlinger,et al.  Amygdala-enriched genes identified by microarray technology are restricted to specific amygdaloid subnuclei , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[53]  I. Torres-Aleman,et al.  Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus , 2001, The Journal of Neuroscience.