We use the rodent auditory system as a tractable model to study how cortical and subcortical circuits process information, adapt to experience, and interact with each other to ultimately drive behavior. We use a variety of approaches to address these questions, including in vivo multichannel electrophysiology, quantitative sensory behavior, slice physiology, optogenetics and viral targeting of defined cell types. Beyond the advancement of basic insight into brain function, the goal of this research is to identify pathophysiological mechanisms associated with sensory disorders, with the hope of translating our findings into novel therapies and treatment strategies.
Current work in the laboratory is focused on the following themes:
Auditory System Dysfunction in Autism Spectrum Disorders
Auditory processing impairments are a defining feature of autism spectrum disorders (ASD) that likely contribute to core ASD phenotypes of altered communication and social behavior. Despite their centrality to the autistic phenotype, we are only beginning to understand the mechanisms driving auditory perceptual deficits in ASD. The auditory system also provides a rich model for examining information processing and plasticity in ASD more generally, as auditory perception involves the coordination of multiple parallel circuits across levels of the CNS that are critically shaped by experience during development. Thus, understanding the mechanistic basis of auditory impairments in ASD will not only help develop treatments for a clinically-pressing and disabling phenotype, but may also uncover fundamental pathophysiological motifs in ASD that will extend across brain areas and cognitive domains. Current research projects on this topic include:
Determining how cortical excitatory and inhibitory imbalance contributes to sound hypersensitivity in rodent models of Fragile X Syndrome (FX)
Examining the coordination between bottom-up and top-down sound processing in FX models
Using novel transgenic rat models to identify convergent pathophysiology at the cellular, synaptic, and circuit level in genetically-distinct forms of ASD
Central Auditory Plasticity in Response to Hearing Loss
The brain has the remarkable ability to modify its connections and adapt its response properties based on prior experience. The auditory system provides an excellent model for mapping experience-dependent synaptic and circuit modifications onto their behavioral consequences. It is imperative, however, to consider both the adaptive and maladaptive potential of this experience-dependent plasticity. For instance, central auditory neurons exhibit homeostatic gain increases aimed at renormalizing activity levels and preserving auditory detection thresholds following abrupt shifts in afferent drive, such as seen with hearing loss. However, we have found that this central gain enhancement can also result in maladaptive changes to sound intensity coding, leading to excessive loudness perception and decreased sound tolerance. These results highlight the perceptual trade-offs that inevitably arise when sensory systems must adapt their neural representations to changes in the environment. Therefore, another central focus of our research is on elucidating the biological mechanisms and behavioral consequences of central gain plasticity in response to hearing loss. This knowledge is crucial for harnessing the brain’s vast potential to compensate for hearing impairment.