Cholinergic systems are implicated in several important brain functions such as learning and memory, visual information processing, arousal, and sleep-wake cycles. In the auditory system, cholinergic innervations have been identified in lower and higher auditory brain regions, including the dorsal cochlear nucleus (DCN), an auditory brainstem nucleus; however, the role of acetylcholine (ACh) on the auditory brainstem remains unknown. Our long-term goal is to determine how ACh shapes network function and representations of incoming sensory information. The objective of our application is to determine the mechanisms underlying cholinergic dependent changes in the synaptic strength of excitatory and inhibitory inputs in the DCN. The central hypothesis of this application is that cholinergic activity modulates synaptic plasticity by changing the strength of endocannabinoid (EC) signaling. In Aim 1 we will identify the cellular mechanisms involved in ACh- mediated modulation of EC signaling. In Aim 2 we will determine the effects of ACh on synaptic plasticity and on the balance of excitation and inhibition in the DCN. Determining the role of cholinergic inputs on the plastic properties of the DCN will not only help us to better understand how ACh influences auditory processing, but it may also lead to a better understanding of disorders caused by neural plasticity-like mechanisms, such as tinnitus. [unreadable] [unreadable] [unreadable] [unreadable]