Synaptic Shortcut

Newly discovered brain pathway overturns anatomy, could solve antipsychotic mystery

Microscopic view of the frontal cortex of a mouse showing the two types of neurons (ChAT+, purple; ChAT-, green) that stem directly from the basal ganglia. Image: Arpiar Saunders and Chip Gerfen

It’s been “known” for decades: Sensory, motor and cognitive signals come in from the brain’s cortex and are processed in the basal ganglia. The basal ganglia then send out signals that get routed through the thalamus and back to the cortex.

Except not always, according to a new study in animal models. The basal ganglia can also talk back directly to the cortex, no thalamus required.

The findings, published this week in Nature, upend classic anatomy and provide possible new insights into psychiatric diseases such as schizophrenia.

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“We’ve discovered a pathway in the brain that nobody knew existed,” said Bernardo Sabatini, the Alice and Rodman W. Moorhead III Professor of Neurobiology at Harvard Medical School and senior author of the study.

“Our results redefine the architecture of the basal ganglia and the mechanisms for subcortical-cortical feedback, which are absolutely crucial for coordinated motor behavior and reward learning,” said the study’s first author, Arpiar Saunders, who conducted the work as a graduate student in the Sabatini lab. Saunders is now a postdoctoral researcher in Steven McCarroll’s lab in the HMS Department of Genetics.

The unexpected shortcut from the basal ganglia to the frontal regions of the cortex also may explain a longstanding mystery about how antipsychotic drugs work, the authors said.

A light in the basement

A light in the basement
Watch Bernardo Sabatini and Arpiar Saunders discuss their discovery of a new pathway in the brain. Video: Stephanie Dutchen