The aim of the proposed research is to explore the neural mechanisms of cellular excitability along the auditory thalamocortical axis. A number of studies have shown that acetylcholine (ACh) can modulate amino acid- mediated synaptic transmission and neuronal excitability in neocortex. The actions of neurotransmitters/neuromodulators such as ACh are implicated in the integrative functions of cerebral cortex that underlie arousal, attention, learning, and memory. In humans, the loss of cholinergic function is associated with a decline in cognitive abilities such as in Alzheimers dementia. The auditory thalamocortical system is characterized by two largely segregated projections known as the lemniscal and non-lemniscal pathways. The two projection systems are thought to exert their excitatory effects through ionotropic NMDA or non- NMDA receptors to glutamate, though the relative importance of these receptor subtypes in thalamocortical transmission is unknown. An in vitro thalamocortical slice preparation will be used to study reciprocal synaptic transmission between the auditory thalamus and cortex. The ultimate goal of the proposed research is to gain a better understanding of the role ACh plays in the synaptic mechanisms that underlie sensory processing between the auditory thalamus and cortex.