Neuronal circuits supporting learning-driven changes in auditory perception. Everyday auditory behavior depends critically on learning-driven changes in auditory perception that rely on neuronal plasticity within the auditory pathway. Discriminative auditory fear conditioning (DAFC), an important form of associative auditory learning, affects the fundamental auditory task of frequency discrimination acuity. While the auditory cortex (AC) is thought to be required for this modulation, how learning shapes frequency discrimination remains unknown. Previous work has largely suggested that the feedforward connections leading up to the AC are the site of this learning-induced plasticity. However, recent research suggests that frequency tuning within the AC itself is shaped by inhibitory-excitatory networks that include multiple morphologically and likely functionally distinct inhibitory interneuron types. Furthermore, the extensive feedback the AC sends to sub-cortical structures, including the inferior colliculus (IC) in the auditory midbrain, may also affect behavioral frequency discrimination. Thus, to dissect the functions of intra-cortical and sub-cortical circuits in auditory learning, we will determine (1) if DAFC affects tone response properties of different neuronal cell types in AC, and how these changes affect frequency discriminability at the neuronal population level in AC; (2) if feedback from AC to the auditory midbrain causally drives learning-mediated changes in auditory behavior. By combining state-of-the-art optogenetic, electrophysiological, behavioral and computational approaches, we are uniquely able to test function of specific circuit elements in awake behaving subjects. The proposed research will, for the first time, identify (1) the effect of auditory learning on specific inhibitory and excitatory neuronal cell types in AC; (2) the role of excitatory-inhibitory circuits in driving changes in frequency discrimination behavior; and (3) the role of cortico-collicular feedback in driving learning-driven changes in auditory frequency discrimination acuity. These important insights into the function of feedback circuits in auditory processing will inform future design of hearing aids and cochlear implants by configuring their outputs for optimal stimulation of these circuits.
The goal of the proposed research is to identify the circuits for auditory learning and perception. This is achieved by using a combination of electrophysiological, optogenetic and behavioral approaches in the mouse system. Verbal communication and auditory navigation require rapid reorganization of the representation of the acoustic environment under varying behavioral demands. Patients with hearing deficits, age-related hearing loss and communication deficits, as well as patients with hearing aids and cochlear implants exhibit extreme difficulty hearing in complex acoustic environments, and transitioning between different environments. Identifying which neuronal circuits underlie the ability to modify the representation of complex acoustic scenes, is a prerequisite for development of new and improvement of existing therapies for these large groups of patients. In particular, these important insights into the function of feedback circuits in auditory processing will inform future design of hearing aids and cochlear implants by configuring their outputs for optimal stimulation of these circuits.
| Angeloni, C; Geffen, M N (2018) Contextual modulation of sound processing in the auditory cortex. Curr Opin Neurobiol 49:8-15 |
| Briguglio, John J; Aizenberg, Mark; Balasubramanian, Vijay et al. (2018) Cortical Neural Activity Predicts Sensory Acuity Under Optogenetic Manipulation. J Neurosci 38:2094-2105 |
| Natan, Ryan G; Rao, Winnie; Geffen, Maria N (2017) Cortical Interneurons Differentially Shape Frequency Tuning following Adaptation. Cell Rep 21:878-890 |
| Wood, Katherine C; Blackwell, Jennifer M; Geffen, Maria Neimark (2017) Cortical inhibitory interneurons control sensory processing. Curr Opin Neurobiol 46:200-207 |
| Blackwell, Jennifer M; Geffen, Maria N (2017) Progress and challenges for understanding the function of cortical microcircuits in auditory processing. Nat Commun 8:2165 |
