Neural circuitry for state-dependent control of cortical auditory processing and perception

Modified Project Summary/Abstract This project will be moved to Rutgers, The State University of New Jersey, New Jersey Medical School beginning September 2018. Behavioral engagement improves perception and learning by managing the limited capacity of the nervous system to process information. Multiple brain regions contribute to controlling behavioral states, in particular frontal cortical structures that play major roles in preparatory engagement. However, the key circuit mechanisms by which specific frontal cortical regions allocate the processing resources of the brain to prospective sensory stimuli remain largely unknown. Consequently, multiple disorders with an attention deficit, such as schizophrenia, autism and ADHD, remain poorly understood and treated. My long-term career goal is to understand the neuronal circuit mechanisms by which the frontal cortex communicates with sensory and neuromodulatory systems to facilitate stimulus processing and to improve behavior, and use this information to guide development of novel treatments. The immediate goal of this proposal is to define neuronal network interactions during preparatory set and to establish causal links with performance. My central hypothesis is that direct and indirect circuits cooperatively control auditory perception by competing mechanisms: direct connections increase evoked responses in auditory cortex (AC) whereas indirect circuits via locus coeruleus (LC) suppress spontaneous and evoked spiking in AC. To accomplish the proposed aims, I will use a combination of powerful neurophysiological, optogenetic and calcium photometry techniques in behaving rats. During the mentored part of this award, I showed that plastic changes in sound representation in the AC can improve perceptual performance, and that preparatory set dynamically modulates evoked and spontaneous firing in AC to control behavior. To determine the circuit mechanism by which preparation controls stimulus representation and performance, I recorded in behaving rats single-unit activity in the medial agranular frontal cortex (maFC), and identified a physiological marker for preparatory set in maFC (Aim 1). During the independent phase that I will conduct at Rutgers University Brain Health Institute, I will investigate synaptic mechanisms and behavioral function of indirect connections between maFC and the AC, with a focus on noradrenergic neuromodulation (Aim 2). For this, I learned complex optogenetic and recording techniques in the Froemke and Buszáki labs at the NYU School of Medicine. My training plan has prepared me to carry out the proposed research and to acquire the skill set and the general knowledge required for my independent career. I am confident that my studies will impart a thorough understanding of circuit interactions regulating behavioral engagement and will enable me to contribute to the development of superior treatments for psychiatric disorders.