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Mriganka Sur
By "rewiring" the developing brain, and by revealing remarkably widespread changes in the adult cortex during learning, Professor Mriganka Sur's lab is proving that the brain is far more plastic and adaptable than anyone believed. Professor Sur is also pursuing innovative responses to human disease such as networks of neurons grown in vitro that could one day serve as "brain grafts" to treat victims of brain injury or stroke.
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 my laboratory is to understand long-term plasticity and short-term dynamics in networks of the developing and adult cortex.
An important way we study plasticity and its mechanisms during development is by rewiring the brain. We induce projections from the eye to innervate nonvisual centers of the brain, 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. Furthermore, visual stimuli that activate the auditory cortex are perceived as visual (rather than as auditory), indicating that the perceptual role of a cortical area can also be shaped by its inputs early in life. We are now examining other functional consequences of the rewiring, such as serial processing in primary and higher rewired cortex, and the molecular substrates by which cortical networks respond to changes in input activity.
One of the molecules that mediates activity-dependent synaptic changes is the NMDA receptor. In a second set of studies, we examine the rules by which patterns of activity lead to functional changes in synapses and structural changes in neurons in the developing visual pathway. We examine synaptic changes during the formation and sorting of connections in the visual thalamus, and changes induced by activity in synapses and spines of cortical cells. We have recently started to examine genes that are expressed uniquely in individual cortical areas, and the ways patterned activity shapes gene expression.
Some of the mechanisms by which activity causes changes in the developing brain are similar to those underlying plasticity in the adult brain. In a third set of studies, we examine plasticity in the adult visual cortex using paradigms that have clear consequences for vision. For example, exposure to tilted contours of a particular orientation causes a short-term shift in the perception of vertical contours, which are seen as tilted away from the adapting orientation. We have shown that the basis for this tilt effect is short-term plasticity in the orientation tuning of neurons in the visual cortex. This plasticity is manifested particularly at certain domains in the cortex, where neurons of different orientations lie in close proximity. Thus, cortical architecture, plasticity and information processing are closely related aspects of cortical function.
My 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, single-cell recording and cortical imaging in alert behaving primates, iontophoresis of transmitter blockers combined with recording, imaging of single neurons in vitro and in vivo using confocal and two-photon microscopy, and microarrays to identify genes in specific tissues.
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