Genomic anatomy of the hippocampus.
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.
Thompson
Carol L
CL
Allen Institute for Brain Science, Seattle, WA 98103, USA.
Pathak
Sayan D
SD
Jeromin
Andreas
A
Ng
Lydia L
LL
MacPherson
Cameron R
CR
Mortrud
Marty T
MT
Cusick
Allison
A
Riley
Zackery L
ZL
Sunkin
Susan M
SM
Bernard
Amy
A
Puchalski
Ralph B
RB
Gage
Fred H
FH
Jones
Allan R
AR
Bajic
Vladimir B
VB
Hawrylycz
Michael J
MJ
Lein
Ed S
ES
D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D002772:Cholera Toxin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D023281:Genomics; D006624:Hippocampus / Q000033:anatomy & histology* / Q000502:physiology*; D021621:Imaging, Three-Dimensional; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism; D025341:Principal Component Analysis; D012688:Septum Pellucidum / Q000033:anatomy & histology / Q000378:metabolism; D013702:Temporal Lobe / Q000033:anatomy & histology / Q000378:metabolism
D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D002772:Cholera Toxin