Knowing a synapse when you see one

Recent years have seen a rapidly growing recognition of the complexity and diversity of the myriad individual synaptic connections that define brain synaptic networks. It has also become increasingly apparent that the synapses themselves are a major key to understanding the development, function and adaptability of those synaptic networks. In spite of this growing appreciation, the molecular, structural and functional characteristics of individual synapses and the patterning of their diverse characteristics across functional networks have largely eluded quantitative study with available imaging technologies. Here we offer an overview of new computational imaging methods that promise to bring single-synapse analysis of synaptic networks to the fore. We focus especially on the challenges and opportunities associated with quantitative detection of individual synapses and with measuring individual synapses across network scale populations in mammalian brain

Canonical Genetic Signatures of the Adult Human Brain

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry