How the visual cortex wires itself—targeted from the start, refined over time
· Medical Xpressby Mike Peña, University of California - Santa Cruz
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A new study led by biologists at the University of California, Santa Cruz, reveals how the primary visual cortex establishes its complex long-range neural networks during early brain development. The study presents a comprehensive, fine-grained map of how the primary visual cortex connects to 11 higher visual areas during development.
The research, published in Cell Reports, was led by Euiseok Kim, associate professor of molecular, cell and developmental biology at UC Santa Cruz. "We systematically mapped how the brain's primary visual area wires itself to 11 higher visual regions over the course of development in mice," said Kim, senior author of the paper and a member of UC Santa Cruz's Institute for the Biology of Stem Cells.
Revisiting a long-standing debate
For decades, neuroscientists have debated how the cerebral cortex—the brain's outer layer—builds the intricate communication pathways required to process sensory information. One dominant theory, known as the "exuberant growth model," proposes that young neurons initially send out excessive connections in many directions, relying on later visual experience to prune away improper pathways.
An alternative model, known as directed guidance, suggests that genetic and molecular signals guide nerve fibers directly to their specific target regions early in development.
By mapping all 11 higher visual target areas simultaneously using advanced viral and molecular tracing techniques, the research team found clear evidence supporting directed guidance. The findings show that targeted, region-specific neural connections are established very early in postnatal development, some of them before the eyes even open.
"The field has had evidence on both sides of a long-standing question," Kim said, "whether this wiring starts out broad and gets refined later through visual experience, or whether it's precise and targeted from early on."
Staggered development across visual regions
Although neural connections are targeted from the start, the study revealed that different visual regions mature on distinct schedules depending on their location along the brain's medial-lateral axis. Medial visual areas receive nerve fibers earlier and refine their connections gradually as the animal grows into adulthood.
In contrast, lateral visual regions receive connections later, undergo a rapid surge of axonal growth and then quickly prune away excess nerve endings to reach mature levels by 24 days after birth, the study found.
The team also found that connections carrying information back to the primary visual cortex form as early as—and in some areas, possibly before—those carrying information forward. This finding challenges the common view that the brain builds its forward pathways first.
Tracking individual neurons with genetic barcodes
To build the map, the team combined several complementary tracing approaches, using engineered viruses to label neurons based on where they send their connections and where their incoming connections originate.
To study circuit development at the level of individual brain cells, the team used MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique developed in Anthony Zador's lab at Cold Spring Harbor Laboratory that can map the connections of thousands of neurons at once.
Individual visual cortex neurons were labeled with unique RNA barcodes that travel along their axons, allowing the researchers to identify where each cell sent its long-distance connections. Repeating this at different ages revealed how these projection patterns changed during development.
Co-first authors Matthew Jacobs and John Ratliff, both researchers in Kim's lab, led experiments showing that individual visual cortex neurons formed the same types of projection patterns at every stage of development examined. Neurons functioned either as dedicated channels projecting to a single region or as broadcasting channels reaching specific combinations of targets, with minimal variation in these wiring motifs over time.
"The data showed us that neurons connect to either a single visual area from the get-go, or to some combination of areas, at predictable rates," said Jacobs, a former postdoctoral researcher in Kim's lab. "We are not seeing cells that connect everywhere randomly and then abandon whole areas during refinement."
A baseline for neurodevelopmental conditions
By clarifying the fundamental principles of how long-range brain circuits form, the study provides a foundation for understanding neurodevelopmental disorders. Disruptions in long-range cortical connectivity during early development have been implicated in conditions such as autism spectrum disorder and schizophrenia.
Kim emphasized the value of now having a comprehensive, fine-grained map of how these neural circuits normally wire up during development. "That matters because atypical wiring during this same developmental window is implicated in conditions like autism," he said. "It sets the baseline that future work on circuit disruption can be measured against, rather than being a finding about autism itself."
The study was co-authored by UC Santa Cruz researchers Alec Soronow, Jordan Nichols, Hylen James, Jorin Eddy and Adam Murray.
Publication details
Matthew W. Jacobs et al, Structured and target-specific development of cortico-cortical connectivity in the mouse visual cortex, Cell Reports (2026). DOI: 10.1016/j.celrep.2026.118027
Journal information: Cell Reports
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