Gene Discovery Links Autism Risk to Specific Brain Circuits

Groundbreaking research uncovers how a gene linked to autism and large head size can rewire brain circuits, causing anxiety and fear behaviors. The findings, published in Frontiers in Cellular Neuroscience, may lead to more targeted treatments for specific autism symptoms.

The PTEN Gene’s Role

Scientists from the Max Planck Florida Institute for Neuroscience found that a gene called PTEN, often associated with autism spectrum disorder (ASD) and brain overgrowth, can significantly alter brain circuits. Variations in PTEN are present in roughly 25% of individuals with autism who also exhibit macrocephaly, making it a key focus in understanding ASD.

The team, led by Dr. McLean Bolton, focused on the central lateral amygdala (CeL), a brain region that controls fear responses. Their work centered on how the loss of PTEN in inhibitory neurons affects the CeL circuit. They discovered these changes create an imbalance that leads to heightened anxiety and fear.

“Although a cell-type specific disruption does not replicate the genome-wide changes seen in humans, it is essential to examine how genetic risk factors operate within distinct neural circuits.”

—Dr. Bolton, MPFI Research Group Leader

Circuitry Changes and Behavior

The researchers utilized a unique circuit mapping approach to measure electrical responses in individual neurons. This method allowed them to map the connections and strengths between neurons. They discovered that deleting PTEN in inhibitory neurons disrupted local inhibitory connections in the CeL by about half. Simultaneously, the strength of excitatory inputs from the basolateral amygdala (BLA) increased.

These changes in brain signaling led to elevated fear learning and anxiety in the mice, but not altered social or repetitive behaviors often seen in ASD. According to the Centers for Disease Control and Prevention, about 1 in 36 children in the U.S. are identified as having autism spectrum disorder (CDC, 2024).

Future Directions

Dr. Tim Holford explained that these findings could help distinguish the specific microcircuits underlying neurological disorders. The team hopes to use other genetic models to determine if these microcircuit changes are convergent changes contributing to heightened fear and anxiety.

The study’s focus on a specific cell type does not replicate all of the changes seen in humans with autism. However, it’s essential to examine how risk factors work within different circuits. Researchers hope that by differentiating these circuits, they can develop focused therapies for specific cognitive and behavioral symptoms associated with neurological disorders.