When we are born our central nervous system consists mostly of unmyelinated axons. As the brain develops, networks of excitatory neurons, inhibitory interneurons and surrounding glial cells are formed. During this time, glial cells called oligodendrocytes extend processes and form concentric circles of membrane (myelin sheaths) around many of these neuronal axons, in a process that is called myelination. Myelination electrically insulates the axons and provides the necessary nutrients that are critical for neuronal health.

Disruptions in network function during brain development are a common feature of many autism spectrum disorders (ASDs). Although much attention is devoted to studying neuronal dysfunction in ASDs, attempts to functionally restore neurons disregarding glia, have only been partially successful. To better treat these disorders, we must take into consideration the crosstalk between neurons and glia.

Modulations of myelin alter the performance of neuronal networks and emerging studies in humans and rodent models point to a “myelin signature” in many ASDs. In addition, many of the genetic factors that are responsible for the development of ASD-related symptoms are also present in oligodendrocytes. Nevertheless, how myelin alterations contribute to the development of ASD-related symptoms is unknown.

Changes in network excitability is a hallmark of ASD pathophysiology and is often attributed to the altered function of inhibitory interneurons. Interneuron axons are myelinated, and their myelin constitutes a substantial fraction of the overall cortical myelin content in rodents and in humans. Our recent work in the adult brain has showed that myelination is critical for interneuron function and survival. Our hypothesis is that defects in interneuron myelination during development disrupt the physiological network function and contribute to the appearance of ASD-related phenotypes.

We are currently using rodent models of ASDs to discover:

The mechanisms that regulate interneuron myelination during normal brain development

The impact of interneuron myelination on network performance

The contribution of cortical myelin in the dysregulation of neuronal networks in ASDs

The effectiveness of myelin modulating strategies in attenuating ASD-related phenotypes.

Our goal is to explore the communication between neurons and oligodendrocytes during brain development, with the hope to reveal new strategies for cellular and functional recovery in autism- associated neurodevelopmental disorders.