Layer 1 interneurons as master regulators of prefrontal cortex circuit development

The brain contains many hundreds of individual cell types which must be connected together to form a normal functional network. If this process occurs normally, it gives rise to our ability to learn, to sense, to move, to plan and to reason. In instances where this process fails it can give rise to devastating neurodevelopmental disorders, such as autism and schizophrenia. To understand brain development we must create a wiring diagram of the brain at different ages and figure out when and how it changes. This proposal aims to determine both by looking at how key cell types regulate circuit formation during precise periods of development. The when is important because brain maturation occurs at different speeds in different brain structures. The period of adolescence is linked to the emergence of our ability to engage in higher-level cognitive tasks such as abstract thought, logic and planning. This coincides with changes in the circuitry of a brain region called the prefrontal cortex. Although we have significant evidence to suggest that the prefrontal cortex changes during adolescence, we still do not understand how this occurs.

Based on previous studies by myself and others I predict that certain key cell types may function as master regulators of development within the prefrontal cortex. These cells are known as layer 1 interneurons and display unique connectivity patterns that allow them to control the activity of a huge number of cells within the local circuit. This connectivity is predicted to help layer 1 interneurons regulate the formation of connections, termed synapses, between individual components of the prefrontal cortex network. This suggests that if we disrupt the ability of L1 interneurons to perform their normal role in the network during key periods of prefrontal cortex development, such as adolescence, it will cause long-term changes to prefrontal cortex network formation and function. The potentially powerful influence of these cell types over...