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Doctor Mriganka Sur

Lecture Abstract

Rewiring Cortex: Plasticity and Specificity of Brain Representations

The function of any area of the neocortex relies on specific input pathways, processing networks, and output projections. Pathways and networks confer representation; how do they arise during development and acquire their functional role? We have used a range of approaches to answer this question. The early development of pathways to and from a cortical area involves the expression of specific genes which regulate molecules that guide axon projections. We have used high-density DNA microarrays to identify genes that are differentially expressed between sensory areas of cortex in neonatal mice (Leamey et al., 2002), and examined the role of a subset involved in output projections. For example, the Ten_m3 gene encodes a type II transmembrane protein and is highly expressed during an early time window only in layer 5 cells within caudal cortex, in a region that corresponds well to visual cortex. Tracer injections into the superior colliculus label cortical layer 5 cells that express Ten_m3, whereas injections into the contralateral visual cortex label layer 5 cells that do not express the gene. Thus, visual cortex cells that lie within the same layer in close proximity but have distinct projections are also molecularly distinct early in development, when pathways are forming.

The development of cortical networks is thought to be regulated by a combination of molecular and activity based cues. However, the classic experiments in this field, such as those demonstrating the effect of lid suture on the visual cortex, have examined the effect of varying the quantity or amount of activity on cortical development. We have shown that varying the quality or pattern of activity has equally dramatic effects of the development of cortical networks. Rewiring the brain in neonatal ferrets and mice by inducing retinal projections to innervate the auditory pathway causes auditory cortex to develop with a very different pattern of activity than normal (Sur and Leamey, 2001). Novel visual inputs significantly alter various aspects of intracortical connections, leading to a map of visual space, orientation selective responses, and an orientation map in the rewired auditory cortex (Sharma et al., 2000) - features that are typical of the primary visual cortex. Thus, the nature of input activity during development importantly shapes cortical processing networks.

Finally, we have shown that the novel projection from the retina to the auditory thalamus can profoundly affect behavior. Rewired ferrets trained to discriminate a visual from an auditory cue can perceive a visual cue as visual when the auditory cortex is activated by vision (von Melchner et al., 2000). Rewired mice rapidly learn a visually cued conditioned fear response, in a time comparable to an auditory cue (and much faster than a visual cue) in normal mice (Newton et al., 2003). Common to these behavioral studies is the explanation that the modality of inputs to the auditory thalamus can instruct the function of subsequent sensorimotor pathways. Thus, brain representations laid down early in development are nonetheless plastic in function, and depend on their inputs for physiological and behavioral instruction.