Sensory representations are dynamically maintained by ascending and descending connections linking the cerebral cortex and the thalamus. Although the overall extent and topographic specificity of descending corticothalamic projections can equal or surpass that of thalamocortical projections, little is known about their role in perception or learning. Here, we propose a new chemical-genetic approach known as DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to parse the functional contribution of corticothalamic circuits that arise from layer 5 versus layer 6 of primay and secondary areas of the auditory cortex. By silencing specific cortical feedback circuits while recording from ensembles of thalamic neurons in mice that are either passively listening to sound or are actively engaged in listening tasks, we will gain deeper insight into the workings of multiple, parallel feedback systems that enable the cerebral cortex to modify its afferent input stream.

Public Health Relevance

On a technical level, these studies will characterize a new approach to remotely silence particular cell types in the brain. This could lead to new, less invasive therapies for neurological disorders characterized by pathological activity levels such as Parkinson's disease, Epileptic Seizure, and Tinnitus. On a conceptual level, these findings could influence the next generation of smart medical technologies that seek to reduce bottom-up data bottlenecks by self-selecting only the information needed to form more valuable predictive models.

National Institute of Health (NIH)
Exploratory/Developmental Grants (R21)
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Auditory System Study Section (AUD)
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Platt, Christopher
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Massachusetts Eye and Ear Infirmary
United States
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Darrow, Keith N; Slama, Michaël C C; Kozin, Elliott D et al. (2015) Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways. Brain Res 1599:44-56
Schreiner, Christoph E; Polley, Daniel B (2014) Auditory map plasticity: diversity in causes and consequences. Curr Opin Neurobiol 24:143-56