The long-term objective of my research is to understand how cortical circuitry processes auditory signals in normal and abnormal conditions. My current interests include understanding functional roles and underlying mechanisms of nicotinic acetylcholine receptor (nAChR-mediated regulation of cortical processing. It's been hypothesized that nAChRs contribute to attention and cognitive function. These behavioral states are compromised, for example, in schizophrenia, dementia, and attention deficit/hyperactivity disorder (ADHD). Schizophrenic patients experience auditory sensory gating deficit and attentional abnormalities, which are corrected by nAChR activation albeit transiently. Loss of nAChRs is prevalent in Alzheimer's type dementia. Patients with this disease may improve auditory and other sensory detection, attention, and processing following treatment with nicotinic agonists. Those affected with ADHD also may find the therapeutic use of nicotinic drugs beneficial to reduce severity. Further studies of nAChR biology will reveal physiological roles of this important class of neurotransmitter receptors and will in turn shed light on development for therapeutic agents. Thalamocortical pathways carry sensory signals critical to cortical neural activity and information processing. Recent experiments implicated that nicotine enhanced auditory thalamocortical transmission in vivo and in vitro. Our preliminary results suggest a novel mechanism of nicotinic enhancement in the thalamocortical system. In the first specific aim, the underlying mechanism of nicotinic enhancement of transmission will be investigated using electrophysiological techniques and a novel brain slice preparation from adult mice. In the second specific aim, anatomical distribution of nAChRs in the thalamocortical pathway will be investigated using laser scanning fluorescence confocal microscopy. The proposed studies will reveal new aspects of thalamocortical information transfer in the adult central auditory system. Nicotine receptors contribute not only to normal auditory signal processing but also to disease conditions with auditory processing impairment such as schizophrenia, dementia, and attention deficit/hyperactivity disorder; however, how nicotine receptors participate in the normal and abnormal information processing is not well known. The proposed studies explore potential mechanisms by which nicotine receptors regulate auditory signals in the brain. [unreadable] [unreadable] [unreadable]