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dc.contributor.advisor Nicolelis, Miguel A.L. en_US
dc.contributor.author Zhang, Hao en_US
dc.date.accessioned 2009-12-18T16:26:39Z
dc.date.available 2011-12-31T05:30:07Z
dc.date.issued 2009 en_US
dc.identifier.uri http://hdl.handle.net/10161/1642
dc.description Dissertation en_US
dc.description.abstract <p>Forebrain cholinergic projection systems innervate the entire cortex and hippocampus. These cholinergic systems are involved in a wide range of cognitive and behavioral functions, including learning and memory, attention, and sleep-waking modulation. However, the <italic>in vivo</italic> physiological mechanisms of cholinergic functions, particularly their fast dynamics and the consequent modulation on the hippocampus and cortex, are not well understood. In this dissertation, I investigated these issues using a number of convergent approaches.</p><p> First, to study fast acetylcholine (ACh) dynamics and its interaction with field potential theta oscillations, I developed a novel technique to acquire second-by-second electrophysiological and neurochemical information simultaneously with amperometry. Using this technique on anesthetized rats, I discovered for the first time the tight <italic>in vivo</italic> coupling between phasic ACh release and theta oscillations on fine spatiotemporal scales. In addition, with electrophysiological recording, putative cholinergic neurons in medial setpal area (MS) were found with firing rate dynamics matching the phasic ACh release. </p><p> Second, to further elucidate the dynamic activities and physiological functions of cholinergic neurons, putative cholinergic MS neurons were identified in behaving rats. These neurons had much higher firing rates during rapid-eye-movement (REM) sleep, and brief responses to auditory stimuli. Interestingly, their firing promoted theta/gamma oscillations, or small-amplitude irregular activities (SIA) in a state-dependent manner. These results suggest that putative MS cholinergic neurons may be a generalized hippocampal activation/arousal network. </p><p> Third, I investigated the hypothesis that ACh enhances cortical and hippocampal immediate-early gene (IEG) expression induced by novel sensory experience. Cholinergic transmission was manipulated with pharmacology or lesion. The resultant cholinergic impairment suppressed the induction of <italic>arc</italic>, a representative IEG, suggesting that ACh promotes IEG induction. </p><p> In conclusion, my results have revealed that the firing of putative cholinergic neurons promotes hippocampal activation, and the consequent phasic ACh release is tightly coupled to theta oscillations. These fast cholinergic activities may provide exceptional opportunities to dynamically modulate neural activity and plasticity on much finer temporal scales than traditionally assumed. By the subsequent promotion of IEG induction, ACh may further substantiate its function in neural plasticity and memory consolidation.</p> en_US
dc.format.extent 4258014 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Neurobiology en_US
dc.subject acetylcholine en_US
dc.subject amperometry en_US
dc.subject hippocampus en_US
dc.subject immediate en_US
dc.subject early gene (IEG) en_US
dc.subject medial septum (MS) en_US
dc.subject theta oscillations en_US
dc.title Forebrain Acetylcholine in Action: Dynamic Activities and Modulation on Target Areas en_US
dc.type Dissertation en_US
dc.department Neurobiology en_US
duke.embargo.months 24 en_US

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