Corticofugal - top-down - pathways from primary auditory cortex (A1) to the auditory brainstem powerfully modulate auditory processing. One important top-down pathway is mediated by corticocollicular neurons: a subset of layer (L) 5 pyramidal neurons in A1 with long-range axonal projections to the inferior colliculus (IC). The corticocollicular projection shapes the response properties of IC neurons, and mediates sound localization learning. However, previous physiological studies of A1 corticofugal mechanisms have not specifically targeted corticocollicular neurons. Therefore, basic physiological properties of corticocollicular neurons, such as their synaptic organization and their cellular properties, remain largely unknown. Our major goal in this proposal is to identify the cell-specific cellular and synaptic mechanisms that determine how L5 corticocollicular and L5 corticocallosal neurons - L5 principal neurons projecting to contralateral cortex - differentially process synaptic and acoustic input. The proposed experimental program will provide fundamental new information about the synaptic, cellular, and microcircuit properties of corticocollicular and corticocallosal L5 neurons. We expect that our findings will establish a new framework for understanding the roles of A1 projection neurons in top-down corticocollicular modulation of auditory processing in normal and disease states, such as in tinnitus and in pathological sound and speech perception.
The proposed research on cellular mechanisms in the auditory cortex is directly relevant to public health because pathology affecting these mechanisms impairs hearing. Here we propose a systematic, quantitative experimental approach to elucidate basic mechanisms and pathways in mammalian auditory cortex at the cellular level. This research is relevant to those aspects of the NIH mission aimed at improving health through understanding pathophysiological mechanisms in disorders causing disability.
|Joshi, Ankur; Kalappa, Bopanna I; Anderson, Charles T et al. (2016) Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex. J Neurosci 36:8487-99|
|Harris, Kenneth D; Shepherd, Gordon M G (2015) The neocortical circuit: themes and variations. Nat Neurosci 18:170-81|
|Joshi, Ankur; Middleton, Jason W; Anderson, Charles T et al. (2015) Cell-specific activity-dependent fractionation of layer 2/3?5B excitatory signaling in mouse auditory cortex. J Neurosci 35:3112-23|