Dr. Edward Callaway gives a special seminar at the Duncan NRI

Feb. 5, 2026 - The Duncan NRI hosted a special seminar by Dr. Edward Callaway, Professor, Systems Neurobiology Laboratory and Vincent J. Coates Chair in Molecular Neurobiology at the Salk Institute for Biological Studies.  His lecture was entitled, "Cell Types and Connections in Cerebral Cortex Linking Transcriptomic Clusters to Cell Types Through Connectivity". 

Abstract

Neural circuits function through complex interactions amongst specific cell types that each contribute uniquely to the generation of perception and behavior. Unique contributions of cell types should be reflected in differences in their connectivity and function. The recent revolution in single cell technologies has led to the identification of more than 5,000 “transcriptomic clusters” in the mouse brain and more than 100 in the cerebral cortex. It is inferred that these clusters, by virtue of their distinct differences in gene expression, might represent distinct cell types. Alternatively, differences in gene expression might reflect redundant gene expression configurations that do not generate differences in connectivity or function. Further, cells within a single transcriptomic cluster might represent more than one cell type based on differences in connectivity or function that emerge through developmental mechanisms that are driven by sensory experience or transient differences in gene expression that do not persist in the adult. To provide better insight into the relationships between transcriptomic clusters and functionally and connectionally distinct cell types, we have developed assays and used them to directly link the connectivity of single neurons to their gene expression and cluster assignments.  Our results show that in the cerebral cortex, the numbers of excitatory cell types with distinct differences in connectivity is far greater than the numbers of transcriptomic clusters. In contrast, for inhibitory cortical neurons, while the numbers of transcriptomic clusters with distinct connectivity is large, for many clusters we do not distinguish differences in connectivity. Across the whole mouse brain, relationships between long-distance axonal projections and gene expression are complex and do not follow straightforward rules. Future studies will benefit from further technological developments to better link gene expression to function at the level of single cells. And developmental studies following changes in the relationships between gene expression, connectivity, and function over time and in the context of differing sensory experience should provide insight into the mechanisms that generate innate and acquired properties of single neurons.