Columbia researcher identifies cellular defect that may contribute to autism

Defect in neuroligin gene disrupts firing of neurons and may result in autism

The causes of autism have long remained a mystery, but new research from Columbia University Medical Center has identified, for the first time, how a cellular defect may be involved in the often crippling neurological disorder.

The research, which is published in today’s issue of Science, examines how a defect in neuroligin genes may contribute to autism. Neuroligins are components of synapses, which connect individual neurons in the brain. The researchers found that the loss of neuroligins perturbs the formation of neuronal connections and results in an imbalance of neuronal function. This imbalance provides an explanation for the neurodevelopmental defects in autistic children.

“Understanding the cellular defects that may underlie autism-spectrum disorders represents an important step towards the goal of providing therapies,” said Peter Scheiffele, Ph.D., assistant professor of physiology and cellular biophysics at Columbia University Medical Center, and principal investigator on the study.

A defect in the neuroligin genes had previously been observed in autistic patients, but its functional significance was not yet understood. Scheiffele’s study showed that in rat neurons without any neuroligin, connections between neurons are altered in a way that is strikingly similar to those found in autistic children.

Each neuron in the brain receives many different inputs – some are excitatory and signal the neuron to fire, and some are inhibitory and signal the neuron to stop firing. Scheiffele’s research team found that neuroligin genes are responsible for regulating the balance between excitatory and inhibitory synaptic function. A defect in neuroligin leads to a selective loss in inhibitory function and thereby impairs the fine-tuning of neuronal connectivity, a neurological problem that is understood to play a role in autism.

“There is much we still don’t know about how neurons connect to each other, but our findings have provided unique insights into what may be going wrong on a cellular level in autistic patients,” said Dr. Scheiffele.