Our previous studies in the dorsal cochlear nucleus (DCN), an auditory brainstem nucleus, have uncovered novel forms of synaptic plasticity that occur at the earliest levels of sensory processing. Our long-term goal is to determine how past experience shapes network function and representations of incoming sensory information. The objective of our application is to determine mechanisms and synaptic rules underlying activity-dependent changes in synaptic strength of excitatory and inhibitory inputs to the auditory brainstem. The central hypothesis of the application is that the concerted operation of opposing forms of long-term synaptic plasticity at synapses onto different cell types in the DCN determines activation and spike timing precision of the output cell. In the first Aim, we will determine the signaling mechanisms and their interactions in shaping the unique types of plasticity observed on the DCN.
In Aim 2, we will investigate the synapse- specific expression of endocannabinoid signaling and its ability to determine different types of synaptic plasticity.
In Aim 3, we will determine the combined effect of different forms of synaptic plasticity on spike timing precision of the output cell. Understanding the mechanisms and role of activity-dependent plasticity in shaping the activity of the DCN circuitry should not only contribute to a unified understanding of the generation of neural responses, but will also have a significant impact on our understanding and cures for disorders caused by neural plasticity-like mechanisms, including tinnitus, hypersensitivity, hyperacousis, age-related hearing loss, and impaired speech discrimination. ? ? ?
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|Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan et al. (2017) Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition. Elife 6:|
|Kalappa, Bopanna I; Tzounopoulos, Thanos (2017) Context-Dependent Modulation of Excitatory Synaptic Strength by Synaptically Released Zinc. eNeuro 4:|
|Yeh, Chung-Yang; Bulas, Ashlyn M; Moutal, Aubin et al. (2017) Targeting a Potassium Channel/Syntaxin Interaction Ameliorates Cell Death in Ischemic Stroke. J Neurosci 37:5648-5658|
|Ceballos, Cesar C; Li, Shuang; Roque, Antonio C et al. (2016) Ih Equalizes Membrane Input Resistance in a Heterogeneous Population of Fusiform Neurons in the Dorsal Cochlear Nucleus. Front Cell Neurosci 10:249|
|Kalappa, Bopanna I; Anderson, Charles T; Goldberg, Jacob M et al. (2015) AMPA receptor inhibition by synaptically released zinc. Proc Natl Acad Sci U S A 112:15749-54|
|Li, Shuang; Kalappa, Bopanna I; Tzounopoulos, Thanos (2015) Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus. Elife 4:|
|Anderson, Charles T; Radford, Robert J; Zastrow, Melissa L et al. (2015) Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc. Proc Natl Acad Sci U S A 112:E2705-14|
|Perez-Rosello, Tamara; Anderson, Charles T; Ling, Cindy et al. (2015) Tonic zinc inhibits spontaneous firing in dorsal cochlear nucleus principal neurons by enhancing glycinergic neurotransmission. Neurobiol Dis 81:14-9|
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