Thompson Carol L, Pathak Sayan D, Jeromin Andreas, Ng Lydia L, MacPherson Cameron R, Mortrud Marty T, Cusick Allison, Riley Zackery L, Sunkin Susan M, Bernard Amy, Puchalski Ralph B, Gage Fred H, Jones Allan R, Bajic Vladimir B, Hawrylycz Michael J, Lein Ed S
Allen Institute for Brain Science, Seattle, WA 98103, USA.
Neuron. 2008 Dec 26;60(6):1010-21. doi: 10.1016/j.neuron.2008.12.008.
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.
基因组规模原位杂交数据的可得性使得对遗传神经解剖结构进行系统分析成为可能。在海马体内，电生理学、损伤及成像研究表明，沿隔颞轴存在功能异质性，尽管精确的潜在神经回路和分子底物仍未明确。将无偏统计成分分析应用于基因组规模的海马基因表达数据，揭示了强大的隔颞分子异质性，从而鉴定出一大批在海马中具有强大区域化表达的基因。对异质性CA3锥体神经元表达模式的手动映射显示，在隔/颞和近端/远端轴上，分子分割意外地复杂，形成了一组相对连贯的九个表达域，其边界相互且不重叠。这些域内粘附分子的独特组合谱表明存在相应的差异连接性，这在使用逆行标记法对CA3投射到外侧隔区的研究中得到了证实。这种复杂的、离散的分子结构为预测海马整个隔颞范围内的功能分化提供了一种新的范例。
