My research interests follow 3 complimentary streams:

  1. Examining different approaches for resetting the circadian clock
  2. Understanding how the heterogeneous assembly of the circadian clock results in a single coordinated rhythmic output
  3. Determining the intracellular effects of various treatments on gene expression and protein regulation.

The circadian clock can be reset by many different treatments, which fall into 2 separate classes: Photic and Non-photic.

Figure 1.

Systemic injections of the serotonin agonist 8-OH-DPAT during the daytime will advance the circadian clock. (Antle et al., J Biol Rhythms, 2003)

Figure 2.

Injections of the adenosine agonist N-CHA into the circadian clock during the daytime will also advance the clock.
(Antle et al., NeuroReport, 2001)

Anatomy of the Circadian Clock

These rhythmic phenomena are regulated by a paired nucleus at the base of the hypothalamus, known as the Suprachiasmatic Nucleus (SCN). The SCN is heterogeneous, consisting of multiple subregions. Two input pathways to the SCN include serotonergic innervation from the median raphe, and Neuropeptide Y input from the Intergeniculate Leaflet. Figure 3.

Two major functional regions of the SCN are the calbindin subregion (in red) and the Vasopressin region (in blue). The Calbindin region receives direct retinal input, responds to retinal signals, and yet is not rhythmic. The Vasopressin region is the location of the clock cells. Cells in this region are rhythmic in gene expression, but do not respond directly to light.

Figure 4.

Neuropeptide Y (green) innervates the ventrolateral SCN. The dorsomedial SCN is at this rostro-caudal level is the location of the oscillating cells, found in a region of the SCN deliniated by Vasopressin (red).

Figure 5.

Serotonin (green) innervates the ventromedial SCN.

Functional responses

Figure 6.

Various treatments can activate cells in SCN. Here cells in green are expressing c-fos, and immediate early gene, after having been exposed to a light pulse early into the night.

Figure 7.

Following a light, clock genes are also expressed in the input region of the SCN. Cells expressing Per1 are labeled here using a non-isotopic form of in situ hybridization.

The current research plans for the lab are to determine what areas of the SCN are affected by the various treatments that reset the circadian clock. Furthermore, the effects at the cellular level in gene expression and protein regulation will be determined with the affected areas