Successful interactions with the environment require some change in behavior to stimuli when their significance changes. Higher neuronal responses have been documented in several brain regions to a significant stimulus, compared to presentation of a non-consequential stimulus. A brain region involved in hearing and that undergoes profound changes (plasticity) during learning about the significance of sensory stimuli is the primary auditory cortex (A1). The experiments of this proposal will begin to reveal the molecular machinery allowing tone-guided behavior and learning-induced plasticity in A1 as rats learn to collect food reward after hearing a tone. It will use a combination of established and cutting edge methods: behavior, to assess learning in rats, will be combined with optical blood flow imaging to identify parts of A1 that respond to a reward-predicting tone and to one that does not, with Arc antisense oligodeoxynucleotide intracranial infusions in A1 to prevent synthesis of Arc protein specifically in A1, and with electrophysiological recordings to assess A1 neuronal responses to tones. It is predicted that rats with suppressed levels of Arc in A1 will learn to collect a food reward after hearing a tone, but will perform poorly the next day. In addition, learning-induced plasticity in A1 is expected to be impaired. To control for non-specific effects of the infusions, the project will compare the behavior and electrophysiological responses to those of rats that have received a scrambled version of the oligodeoxynucleotides. The findings will contribute to understanding the molecular underpinnings of auditory learning and consolidation of associated A1 plasticity. This research will help scientists at the undergraduate, graduate and postdoctoral level acquire highly integrative thinking and skills. It will also establish, by collaborating with local minority-serving colleges, a website for neuroscience education with grade-appropriate content for students K8-college, including those with hearing impairments.
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. With the help of this NSF grant, we have shown 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 showing decreased responsiveness, while others showing increased responsiveness. We further started investigating the neuromodulatory and molecular mechanisms underlying this diverging plasticity. We demonstrated that the increased responsiveness is driven by acetylcholine acting through the nicotinic acetylcholine receptors. Importantly, we showed that the enhancement and suppression that occur concurrently rely on the learning-induced synthesis of a protein necessary for synaptic plasticity and learning, Arc. Further work is needed to determine the molecular partners of Arc that allow some synapses to enhance behaviorally-driven responsiveness, while others- to suppress it. With the presently collected data we have 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. We have assembled a working team that includes students from several local universities with two goals: 1) to enhance the students’ educational experience through deeper understanding of cortical plasticity and methods of research, and 2) to develop a public resource- a website with several age-appropriate sections that introduce cortical plasticity and cortically-supported learning and memory.
