Pituitary Adenylate Cyclase -Activating Peptide Signaling in the Mouse Circadian Clock

Results from a variety of sources suggest a role of pituitary adenylate cyclase-activating peptide (PACAP) in light/glutamate-induced phase resetting of the circadian clock, yet the particulars of this role remain controversial. Mice generated by Lee Eiden and colleagues that do not express PACAP were examined to test the hypothesis that PACAP plays a physiological role in light or glutamate-induced circadian clock resetting. Both behavioral measurement of wheel-running and electrophysiological measurements of spontaneous electrical firing rate rhythms show a selective alteration in late-night clock resetting in transgenic mice, compared with their PACAP-competent cousins. This alteration in the resetting profile of PACAP-null mice is manifest despite the absence of any measurable change in the endogenous period of circadian rhythms. The suprachiasmatic nucleus (SCN) of the hypothalamus is the mammalian circadian pacemaker, which can be studied in an isolated slice preparation. Measurement and replacement of glutamate-induced signaling components to the SCN slice indicate that a permissive contribution of PACAP affects glutamate-induced signaling components downstream of cGMP. Concentration-dependent PACAP modulation of glutamate-induced shifting was supported by PACAP/glutamate co-administration to the isolated SCN slice. Together these experiments indicate that PACAP plays a number of intersecting roles that modify light/glutamate-dependent circadian clock resetting. A model is proposed that describes the current understanding of these intersecting pathways.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Lindberg, Peder Todd

Contributors dc:contributor

• Gillette, Martha U.

• Biology, Neuroscience

Language dc:language

eng

Identifier

(MiAaPQ)AAI3202131

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82506