The auditory system is often challenged with the task of assigning behavioral meaning to sounds: the cry of an infant immediately commands your attention, a fire alarm signals the need for a hasty departure, and the familiar sound of your cell phone causes an early exit from a meeting. How does the brain accomplish this seemingly effortless feat? A network of regions in the brain are implicated in the act of auditory perception, but even regions thought to be primarily concerned with the representation of sounds have cells that seem unmoved by the behaviorally-relevant acoustic inputs. These ?nominally non-responsive cells? are highly prevalent, underexplored, and may provide key insights into how the brain accomplishes auditory-related learning and contextualizes audition. For example, there is emerging evidence that these cells are important for generating flexible behaviors. Developing a systems-level understanding of these widely observed but rarely analyzed neurons is essential for relating auditory-related behavior to neural activity in the auditory pathway and may yield critical insights into rehabilitation strategies for cochlear-implant (CI) users as CI stimulation can result in highly variable cortical activation. This proposal will investigate the role nominally non-responsive cells play in auditory perceptual behaviors by recording and decoding from auditory cortex, an area downstream (an auditory domain of the frontal cortex), and an area upstream (the medial geniculate nucleus of the auditory thalamus) during behavior. This proposal leverages cutting-edge electrophysiological recordings in behaving rats, optogenetics, and a novel single-trial decoding algorithm for evaluating cells with complex response profiles to address the following aims: characterize the contribution of nominally non-responsive auditory cortical neurons to auditory behavior (Aim 1); determine how auditory behavioral variables are represented and modulated along the auditory pathway by nominally non-responsive neurons (Aim 2); and determine how the activity of nominally non- responsive neurons dynamically reflects the behavioral meaning of sounds (Aim 3). The results from this work will provide significant insight into how animals compute the behavioral significance of sounds. Clarifying the specific role each auditory station plays in generating auditory-relevant behaviors will have implications for (1) improved diagnosis and treatment of hearing deficits caused by disease or injury and (2) improved auditory prosthetic devices that stimulate multiple brain regions to enhance auditory perception. An experienced team of mentors and collaborators will provide training critical for the candidate's short- and long-term success, including: chronic recordings, optogenetics, LFP analysis and single-trial decoders. The proposed training program combines hands-on training, mentorship, coursework, seminars, and professional meetings. In the long-term, this support will equip the candidate to lead a laboratory that merges analytical and systems approaches to explore the role of nominally non-responsive activity to auditory behavior.
Throughout life the brain is remarkably plastic?it can rapidly adapt to ever-changing environments or circumstances. This is particularly true for the auditory system, which enables language learning, and general forms of auditory processing required for normal behavior. However, the neural mechanisms underlying how the central auditory system dynamically computes the behavioral significance of sounds is unknown; furthermore, it is unclear how disorders like autism, dyslexia, aphasia, and other communication disorders commandeer these mechanisms to produce pathological states. The results from the proposed experiments will provide critical insights into improved diagnosis and treatment of hearing deficits caused by disease or injury and will inform targeted therapies for central auditory processing disorders.
|Ebbesen, Christian L; Insanally, Michele N; Kopec, Charles D et al. (2018) More than Just a ""Motor"": Recent Surprises from the Frontal Cortex. J Neurosci 38:9402-9413|