CONDITIONING RELATED NEUROTRANSMITTER RELEASE IN NEOCORTEX

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The long-term objective of these studies is to define in sensory cortex, the differential physiological roles of subcortical neurotransmitter/neuromodulator (neurotransmitter) systems which project in a diffuse manner to neocortex (i.e. acetylcholine (ACh), norepinephrine (NE), serotonin and dopamine); the proposed studies will focus on the pattern of conditioning-related ACh and NE release in auditory cortex. These studies should be viewed as preliminary; however, data from the proposed experiments should aid in providing a basis for understanding the cognitive and memory alterations associated with age- and/or disease-related alterations of neurotransmitter function in cortex. Such information is prerequisite to the rational design of therapeutic agents for use in Alzheimer's Disease and related disorders where cortical neurotransmitter function is compromised. The specific aims of the proposed studies are to: 1. Characterize the effect of sensitization training, associative conditioning, extinction and re-development on ACh release in auditory cortex. 2. Initiate studies to determine the pattern(s) of conditioning-related release of biogenic amines in rat auditory cortex. 3. Provide a laboratory environment to be used in the training of potential neuroscientists, with an emphasis on under-represented minorities. All experiments will be conducted in the urethane anesthetized rat. Pure tones will be paired with rewarding medial forebrain bundle (MFB) stimulation for conditioning. ACh release will be sampled in auditory cortex ipsilateral to MFB stimulation with microdialysis and analyzed with HPLC and electrochemical detection. Multi-unit neuronal activity will be recorded with low resistance glass microelectrodes. NE will be measured using in-situ electrochemistry.