Cortical Development, Plasticity and Dynamics

Mriganka Sur, PhD, Principal Investigator

Plasticity, or the adaptive response of the brain to changes in inputs, is essential to brain development and function. The developing brain requires a genetic blueprint but is also acutely sensitive to the environment. The adult brain constantly adapts to changes in stimuli, and this plasticity is manifest not only as learning and memory but also as dynamic changes in information transmission and processing. The goal of our laboratory is to understand long-term plasticity and short-term dynamics in networks of the developing and adult cortex.

Cortical development starts with genes that demarcate different areas, and subsequently genes that lay a scaffold of connections between neurons in each area. We use microarrays to discover genes that underlie cortical patterning and connectivity, followed by molecular and physiological tools to examine the function of these genes and the interactions between them and the environment.

We use two model systems for studying developmental plasticity and its mechanisms. The first, which we pioneered, involves rewiring the brain: we induce projections from the eye to innervate nonvisual centers, such as the auditory thalamus, early in life. Since visually evoked electrical activity has a different spatial and temporal structure than auditory activity, visual inputs cause the auditory pathway to develop with a very different pattern of activity than normal. We have demonstrated that this profoundly alters neuronal networks and connectivity in the rewired auditory cortex. We are now examining other functional consequences of the rewiring, and the molecular substrates by which cortical networks respond to changes in input activity.

The second model system involves the formation and maintenance of ocular dominance columns in visual cortex. Here, we examine the dynamics of rapid structural changes that accompany rapid functional changes in the strength and location of connections. Specific molecules, such as actin in the cytoskeleton and plasmin in the extracellular matrix, are key players that cause changes in neuronal connectivity due to changes in electrical activity.

Some of the mechanisms by which activity causes changes in the developing brain are similar to those underlying plasticity in the adult brain. We examine plasticity in the adult visual cortex using both "bottom up" and "top down" paradigms. These studies link cortical networks, plasticity and information processing as closely related aspects of cortical function.

Our laboratory uses state-of-the-art techniques. These include multiple electrode single unit recording in cortex, high resolution optical imaging of activity from an expanse of cortex, whole-cell intracellular recording in slices and in the intact brain, imaging of single neurons in vitro and in vivo using confocal and two-photon microscopy, and microarrays and computational tools to identify genes in specific tissues.