Saturday, March 15, 2025
3/15/2025
PROJECT SUMMARY Training can sharpen and refine our perceptual skills. In the auditory system, this process— termed perceptual learning— shapes the acquisition of both native and non-native languages, and can improve speech and music recognition in users of assisted listening devices. Previous work has highlighted important contributions of non-sensory processes (such as attention and reward) to perceptual learning, but the underlying neural circuit mechanisms remain poorly understood. Recent evidence suggests the involvement of the orbitofrontal cortex (OFC), a prefrontal cortical region implicated in signaling reward and expectation, and in exerting top-down control of sensory cortical processing. This project will explore the contribution of the OFC to auditory perceptual learning in a classic model organism for auditory studies, the Mongolian gerbil. Our overarching hypothesis, informed by previous and ongoing work, is that training on an auditory task strengthens a descending projection from the OFC to the auditory cortex, leading to gradual improvements in auditory cortical sensitivity that underlie perceptual learning. We propose three specific aims to test this hypothesis. In Aim 1, we use multichannel electrophysiology and pathway-specific fiber photometry to determine whether training on an auditory task strengthens a descending projection from the OFC to auditory cortex by increasing presynaptic activity. In Aim 2, we combine pharmacological and optogenetic methods to determine whether the OFC modulates auditory cortical processing and/or perception in behaving animals via a descending monosynaptic projection, and reveal whether this capability is enhanced after perceptual learning. Finally, in Aim 3 we determine whether optogenetic activation of auditory cortical-projecting neurons in the OFC is sufficient for improving auditory cortical and perceptual sensitivity in behaving animals in the absence of training. In summary, our experiments combine a powerful array of in vivo tools to dissect the neural circuit mechanisms that support auditory perceptual learning. The importance of perceptual learning for improving auditory skills in hearing impaired listeners, and the disruption of perceptual learning in individuals with neurodevelopmental disorders, like dyslexia and autism, highlight an urgent need for a more complete description of how perceptual learning is implemented in the brain.
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