A nearly universal and important property of neuronal responses in the auditory pathway is adaptation to the stimulus, such that the neuronal responses to the same sound depend on the context in which the sound is presented. In central auditory pathway, neurons exhibit stimulus-specific adaptation (SSA), responding to the same tone more weakly when the tone is presented frequently, than when the tone is presented rarely. SSA is fundamentally different from adaptation found earlier in the auditory pathway, because it does not generalize across all inputs to a neuron, and therefore cannot be explained by a generalized reduction in excitability of the neuron. The mechanisms that give rise to SSA in the auditory pathway are not well understood.
In specific aim 1, we test the hypothesis that two types of inhibitory interneurons facilitate SSA in the auditory cortex in a complementary fashion.
In specific aim 2, we test the hypothesis that the auditory cortex provides SSA to the auditory midbrain. Understanding the mechanisms that give rise to SSA is important because SSA have been linked to detection of deviant sounds, a process that contributes to sound source separation and object grouping. However, a direct link between SSA and detection of deviant sounds has not been established.
In specific aim 3, we test the hypothesis that SSA in the central auditory pathway facilitates detection of deviant sounds. Impact: Through innovative optogenetic, electrophysiological, and behavioral methods, the proposed research will (1) identify novel neuronal mechanisms that facilitate adaptation in the auditory pathway; (2) dissociate the functional roles of distinct cortical inhibitory circuits and cortico-collicular feeback in auditory processing; and (3) provide a direct test of these circuit elements in auditory perception.
The goal of the proposed research is to identify the circuit-level mechanisms in the central auditory pathway that underlie selective adaptation to frequent sounds and to test the way these mechanisms contribute to behavioral detection of deviant sounds. This is achieved by using a combination of electrophysiological, optogenetic and behavioral approaches in the mouse system. Patients with hearing deficits, age-related hearing loss and communication deficits, exhibit disproportionate difficulty hearing when several sound sources are present. Identifying the function of specific neuronal circuits in the auditory pathway and their relation to deviance detection, which has been implicated in auditory source segregation, is a prerequisite for development of new and improvement of existing therapies for these large groups of patients.
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| 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; Carruthers, Isaac M; Mwilambwe-Tshilobo, Laetitia et al. (2017) Gain Control in the Auditory Cortex Evoked by Changing Temporal Correlation of Sounds. Cereb Cortex 27:2385-2402 |
| Blackwell, Jennifer M; Geffen, Maria N (2017) Progress and challenges for understanding the function of cortical microcircuits in auditory processing. Nat Commun 8:2165 |
| 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; Taillefumier, Thibaud O; Natan, Ryan G et al. (2016) Stable encoding of sounds over a broad range of statistical parameters in the auditory cortex. Eur J Neurosci 43:751-64 |
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| Aizenberg, Mark; Mwilambwe-Tshilobo, Laetitia; Briguglio, John J et al. (2015) Bidirectional Regulation of Innate and Learned Behaviors That Rely on Frequency Discrimination by Cortical Inhibitory Neurons. PLoS Biol 13:e1002308 |
| Mwilambwe-Tshilobo, Laetitia; Davis, Andrew J O; Aizenberg, Mark et al. (2015) Selective Impairment in Frequency Discrimination in a Mouse Model of Tinnitus. PLoS One 10:e0137749 |
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