Genomic Anatomy of the Hippocampus

Carol L. Thompson, Sayan D. Pathak, Andreas Jeromin, Lydia L. Ng, Cameron R. MacPherson, Marty T. Mortrud, Allison Cusick, Zackery L. Riley, Susan M. Sunkin, Amy Bernard, Ralph B. Puchalski, Fred H. Gage, Allan R. Jones, Vladimir Bajic, Michael J. Hawrylycz, Ed S. Lein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

242 Scopus citations

Abstract

Availability of genome-scale in situ hybridization data allows systematic analysis of genetic neuroanatomical architecture. Within the hippocampus, electrophysiology and lesion and imaging studies demonstrate functional heterogeneity along the septotemporal axis, although precise underlying circuitry and molecular substrates remain uncharacterized. Application of unbiased statistical component analyses to genome-scale hippocampal gene expression data revealed robust septotemporal molecular heterogeneity, leading to the identification of a large cohort of genes with robust regionalized hippocampal expression. Manual mapping of heterogeneous CA3 pyramidal neuron expression patterns demonstrates an unexpectedly complex molecular parcellation into a relatively coherent set of nine expression domains in the septal/temporal and proximal/distal axes with reciprocal, nonoverlapping boundaries. Unique combinatorial profiles of adhesion molecules within these domains suggest corresponding differential connectivity, which is demonstrated for CA3 projections to the lateral septum using retrograde labeling. This complex, discrete molecular architecture provides a novel paradigm for predicting functional differentiation across the full septotemporal extent of the hippocampus.

Original languageEnglish (US)
Pages (from-to)1010-1021
Number of pages12
JournalNeuron
Volume60
Issue number6
DOIs
StatePublished - Dec 26 2008

Keywords

  • MOLNEURO
  • SYSBIO
  • SYSNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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