Learning and memory processes in the adult are diverse and rely on different brain structures. Adult perceptual learning allows an organism to survive by adapting its responses to salient sensory stimuli in its environment, such as salient sounds, and relies on intact function of the primary auditory cortex (A1). Neither the time course, nor the molecular mechanisms underlying this form of learning are currently known. Previous work supported by NSF showed that, unlike the current notions of A1 plasticity during auditory perceptual learning, the early stages are marked with a wide-spread reshaping of A1 with some areas of decreased, while others of increased responsiveness. Importantly, these opposing, but concurrently-occurring, changes rely on the learning-induced synthesis of a protein necessary for synaptic plasticity and learning, Arc. A primary goal here is to elucidate the molecular mechanisms of how Arc interacts with several other proteins to simultaneously direct these divergent changes. The hypothesis is that decreased responsiveness is due to interactions with proteins that enhance endocytosis of receptors that increase synaptic excitability, while enhancement of responses is due to Arc's interaction with other proteins leading to dendritic spine reshaping. This idea will be tested by assessing the relative abundance of these proteins in areas with electrophysiologically-documented decrease or increase of responsiveness, respectively. Other predictions of the model will be tested by measuring the electrophysiological responses across A1 at different stages of learning. The data will be used to create a computational model of perceptual learning. The broader impact of this work includes involvement of minority undergraduates from several disciplines, as well as professional training of postdoctoral fellows. Developing a working team that includes students from several local universities will result in developing a public resource, a website with several age-appropriate sections that introduce cortical plasticity and cortically-supported learning and memory.
