Schematic representation of the diverse cellular effects of transmeningeally delivered muscimol in the neocortex and the multiple clearance mechanisms for the cortically diffused molecules. Note that muscimol exerts its primary neuronal effects via GABA-A receptors located postsynaptically on both pyramidal cells and interneurons and presynaptically on both subcortical and intracortical afferent fibers. Besides clearance through cerebrovascular circulation, nonspecific glial uptake and local extracellular metabolism may also contribute to muscimol removal.