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<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>
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