Top-down dynamics in autism

  • Awarded: 2015
  • Award Type: Research
  • Award #: 345229

Autism can be thought of as a dysfunction in the interaction between cortical areas, particularly the top-down interactions that enable us to select features of our environment that are relevant for the task at hand and to suppress features that are task-irrelevant. Charles Gilbert and his colleagues at Rockefeller University propose a combination of behavioral and high-resolution imaging experiments to study the mechanisms of autism at the level of the circuitry of the cerebral cortex in animal models of autism.

Their experiments are designed to determine the mechanisms by which the genetic mutations that have been linked to autism produce the behavioral deficits in the disorder. Establishing this linkage requires understanding the role these mutations play in disrupting the normal function of cortical circuits. By studying animal models that are both genetically tractable and capable of training in complex perceptual discriminations, the researchers can determine the influence of autism-related mutations on perception and on the operation of cortical circuits.

Gilbert and his team plan to combine two-photon microscopy, a high-resolution imaging technique, with genetically encoded fluorescent sensors of neural activity to monitor the function of ensembles of neurons and axons; the patterns of activity in wildtype and mutant mice will be compared.  Such an experimental approach will enable the researchers to determine the aberrations in cell signaling — both within and between cortical areas — that are associated with mutations that have been identified in individuals with autism. The animal studies can then be used as a basis for doing psychophysical measurements of perceptual function in human cohorts, and potentially for developing perceptual training paradigms to remediate the dysfunction of cortical processing occurring in autism.

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