Controlling, Mapping, and Modeling Neural Circuits

## Genes, RNA, and cell types **Genes** are DNA instructions. When a gene is used, it is copied into **RNA** — this is **gene expression**. The full set of RNAs in a cell is its **transcriptome**. Neurons that express similar sets of genes are grouped into a **cell type**. Cell types differ in their shape, connections, and roles. ## The spatial problem Two traditional approaches each lose something: - **RNA sequencing** of dissociated cells measures thousands of genes per cell, but the tissue is broken apart — so we lose **where** each cell was. - **Imaging** keeps each cell in place, but historically measured only a few genes at a time. Location matters: the same cell type can play different roles in different regions, and neighbors influence each other. ## STARmap **Spatial transcriptomics** measures gene expression while keeping tissue location. **STARmap** is a method of this kind developed for intact tissue: RNA molecules are converted into amplified, readable signals inside a hydrogel-embedded sample and read out by imaging, cell by cell, across many genes. Conceptually: **molecular identity + spatial location, inside tissue.** ## Building the bridge STARmap lets researchers connect: **cell type + location + activity + behavior** For example, combining activity markers or recordings with spatial gene-expression maps can show which molecularly defined cells, in which positions, were engaged during a behavior. This links the "genes" and "cell types" levels of the course framework to circuits and behavior. ## The course framework GENES → CELL TYPES → CIRCUITS → NETWORK DYNAMICS → BEHAVIOR, studied by four complementary approaches: **map**, **record**, **perturb**, and **model**. Understanding a neural circuit requires several of these ways of observing and testing the same biological system. ## Further reading - [Deisseroth Lab (Stanford)](https://web.stanford.edu/group/dlab/) - Developmental xenocortication using human-derived organoids in mice. *Nature* (2026) — collaborative work by multiple Stanford groups and investigators.