Home
Tags
No Tags
REGULATION OF NON-PHOTIC PHASE-RESETTING OF THE MAMMALIAN CIRCADIAN CLOCK
| Title: | REGULATION OF NON-PHOTIC PHASE-RESETTING OF THE MAMMALIAN CIRCADIAN CLOCK |
| Author: | Grossman, Gregory H |
| Description: | The suprachiasmatic nucleus (SCN) of the hypothalamus is the principle mammalian endogenous biological oscillator, generating and orchestrating a myriad of circadian rhythmic events and processes. This autonomous pacemaker can be entrained by both environmental cues (primarily via fluctuations in the light/dark cycle), as well as organismal influences (internal state feedback information), in order to coordinate and synchronize internal biochemical functions to solar time, which allows the organism to anticipate and therefore, prepare for upcoming events or tasks rather, than reflexively reacting to stimuli in the environment. In the present study we primarily utilized in vivo techniques to examine the regulation of non-photic (all stimuli other than light or the chemical events associated with photic signaling) phase-resetting of the circadian clock. The monoamine, serotonin (5-hydroxytryptamine; 5-HT) is a well described neurotransmitter in the central nervous system of vertebrates. Though it is discretely synthesized in the raphe complexes of the mid-brain, it is released from terminal fields of collaterals that innervate various portions of the brain and spinal cord. Its role in mediating non-photic-induced phase-alterations in the clock, as well as the respective output rhythms generated by the clock, has been investigated. However, it remains speculative if endogenous serotonergic signaling directly in the area of the clock, or in other regions of the circadian system is necessary and or sufficient to cause 2 phase-shifts. HPLC analysis of samples collected by in vivo microdialysis, provides the first direct evidence that general arousal, in the absence of vigorous locomotor activity, is sufficient to induce 5-HT release in the SCN, which is mediated by the activation of the dorsal raphe nucleus (DRN). The results also demonstrate that inhibition of the DRN, attenuates phase-shifts associated with activity. In addition, the results constitute the first direct evidence that activity/arousal induces 5-HT release in a brain region that has direct connections to the SCN, the intergeniculate leaflet (IGL), and that the release is also coupled to the activation of the DRN. The finding that an exogenous 5-HT agonist locally targeted in the IGL induces shifts in rhythms similar to activity/arousal behaviorally-induced shifting further implicates 5-HT in phase-alterations. In addition, post synaptically blocking 5-HT signaling in this region attenuates shifts associated with behavioral manipulations. In general, these results provide evidence that the serotonergic system plays a critical role in the regulation of non-photic phase-resetting of mammalian circadian rhythms. |
| Permanent Link: |
http://rave.ohiolink.edu/etdc/view?acc_num=kent1164046548
http://hdl.handle.net/2374.OX/17722 |
| Date: | 2006 |
Files in this item
| Files | Size | Format | View |
|---|---|---|---|
|
There are no files associated with this item. |
|||