AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

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DESCRIPTION (provided by applicant): The basal forebrain (BF), a complex brain region that contains cholinergic and various non-cholinergic corticopetal neurons and interneurons, plays an important role in modulating cortical activity. Corticopetal BF projections, especially the cholinergic component, have been implicated in memory, attention, and many other cognitive processes. While the cholinergic corticopetal component received particular emphasis, very little is known about non-cholinergic components of the corticopetal projection, with special reference to putative glutamatergic neurons, and the local information processing in the BF. In this proposal we will investigate: 1) whether or not the neuronal subtypes of the BF include cortically projecting glutamatergic cells, 2) what the local target(s) of the axon collaterals of NPY interneurons are. 3) Whether or not local NPY-containing neurons also receive prefrontal input. In these experiments morphological (single cell staining, immunocytochemical marking, in situ hybridization and anatomical tracing, both at the light and electron microscopical levels) will be combined with electrophysiological (single unit and EEG) techniques. In additional studies, we will investigate, in a systematic fashion, how architectural features at the network level would enable the basal forebrain corticopetal system to participate in coordinating association and sensorimotor functions. For example, we will test the hypothesis that neurons in the BF which project to interconnected somatosensory (S1, S2) and motor cortical areas (M1), and which cooperate with each other during somesthesis-guided behaviors, show larger overlap than projections to neighboring cortical areas that, in turn, represent non-contiguous body-parts. In these experiments, we will use dual retrograde tracer injections into electrophsyiologically identified sensory or motor cortical representations and retrogradely labeled cholinergic and non-cholinergic neurons in the BF will be analyzed for segregation or overlap. These studies will have significant impact on our understanding of information processing in basalo-cortical networks, and concomitantly the understanding of the aberrant information processing in these networks that characterize several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and drug abuse.