The proposed experiments involve the use of in vivo microdialysis and high-performance liquid chromotography/electrochemical detection techniques to measure the amount of the neurotransmitter acetylcholirie (ACh) released from the corticopetal projections of the nucleus basalis magnocellularis into primary auditory (A1) and visual (V1) cortices in the rat brain during various Pavlovian associative learning paradigms.
The specific aims of these experiments are (1) to demonstrate the relationship between ACh release in task-relevant sensory cortices and the strength of conditioned responding to modality-specific sensory stimuli, (2) to provide evidence for the existence of a differential, regionally-specific pattern of ACh release (as opposed to a generalized, global pattern of release), where the greatest levels of ACh are released in task-relevant sensory cortices during associative learning, and (3) to determine whether manipulating demands on attentional processing of conditioned stimuli causes increases or decreases in the amount of ACh released in the sensory cortex corresponding to the affected conditioned stimulus. These goals will be achieved through a series of three experiments where ACh release will be simultaneously measured in A1 and V1, and where conditioned appetitive approach behavior will be quantified in a classical conditioning paradigm (Experiment 1), an incremental attentional processing paradigm (Experiment 2), or in a blocking paradigm (Experiment 3). Developing this novel model of selective attention and associative learning will provide important insight into the brain mechanisms involved in attention, in cortical synaptic plasticity, and in memory formation itself. Furthermore, results from these experiments will contribute to ongoing research in diverse areas of medicine and neuroscience, ranging from the study of Alzheimer's disease (characterized by cortical ACh deficiency and memory impairments) to reorganization of cortical function following peripheral nerve injury (where such reorganization depends on cortical ACh).
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