The Earth's pervasive 24 hr light/dark cycle has resulted in a fundamental rhythmicity in nearly all living organisms. This rhythmicity depends on the synchronization of endogenous circadian oscillators (i.e. entrainment), but also the direct influences of environmental timing cues (i.e. masking), such as light. In the mammalian circadian system, it is well established that the suprachiasmatic nucleus (SCN) is the central pacemaker whose signals contribute to temporal regulation of numerous physiological and behavioral processes. Using anatomical tract-tracing and electrophysiological techniques, I describe a novel output pathway from SCN to ventral tegmental area (VTA), a midbrain nucleus with a pivotal role in motivation and arousal. Chapter two will delineate the anatomical structure of this SCN-VTA circuit. Using the trans-synaptic, retrograde tract tracer, pseudorabies virus (PRV; Bartha strain), I found there exists a synaptically linked circuit from SCN that impinges on VTA through the medial preoptic nucleus (MPON). Using single-unit, extracellular recording techniques in the anesthetized rat, I further characterized resulting diurnal and circadian fluctuations in VTA impulse activity. Chapter three describes a novel population of VTA neurons that selectively fires during the active circadian phase. These neurons were fast-firing, low-bursting, with wide action potential widths, and were non-responsive to footpad stimulation. Neurochemically, they were non-dopaminergic, non-GABAergic, but sensitive to changes in dopaminergic neurotransmission. Chapter four describes diurnal and circadian variations in classic dopaminergic and GABAergic VTA neurons. The two cell types were differentially influenced by the daily cycle with a unique pattern of topographically and functionally segregated populations firing a different phases. At one level, the results of this thesis present a novel synaptic circuit, which may drive organisms' adaptations to the ubiquitous 24 hr cycle. At another, they increase our appreciation for the immense complexity of the ventral tegmental area, both at a cellular and functional level.
|School:||University of Pennsylvania|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 68/04, Dissertation Abstracts International|
|Keywords:||Circadian rhythm, Suprachiasmatic nucleus, Ventral tegmental area|
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