Basic Science Research

Anatomy and Development

Role of the Retinal Projection in the Organization of the Suprachiasmatic Nucleus
and the Functioning of the Circadian System
Lois K. Laemle, PhD

The suprachiasmatic nucleus generates circadian rhythms, which are entrained (synchronized) to environmental light-dark cycles by the retinohypothalamic tract (RHT)—a direct projection from the retina to the suprachiasmatic nucleus. Malfunctions of this system have been linked to jet lag, sleep disorders, and seasonal depression. The laboratory of Dr. Leamle is presently using behavioral, anatomical, immunocytochemical, neurophysiological, and pharmacological methods to probe the role of the RHT, and that of secondary visual projections, in the development and organization of the suprachiasmatic nucleus and circadian rhythms. In vitro slice preparations have shown that spontaneous activity of SCN pacemaker neurons is indistinguishable in an anophthalmic laboratory model and its sighted control. The marked differences in neuronal output are due to an increase in GABAergic terminals on pacemaker neurons of the anophthalmic model.

These studies use an anophthalmic laboratory model system and focus on the roles of genetic programming and environmental factors. Dr. Laemle’s team has identified and sequenced the gene that causes anophthalmia in this laboratory model and shown its homology with similar genes in rat, xenopus, and man. They have described the role of programmed cell death (PCD) in normal ocular development and identified alterations in temporal and spatial parameters of PCD in anophthalmic laboratory models.

The study tests 2 hypotheses: (1) In congenitally blind subjects, brain regions that would normally process visual information have been reprogrammed to process and augment other sensory modalities, primarily auditory and to a lesser extent, somatosensory or touch; (2) Reprogramming of the visual system can be enhanced by an auditory- and/or somatosensory-enriched environment.

This research program addresses a variety of topics specifically focused on issues of a developmental nature: (1) The development of a characteristic vasculature in the limb bud (pattern formation in normal and abnormal limb vasculogenesis); (2) the distribution of angioblasts within limb mesenchyme; (3) the nature of transient vascular networks (regression and remodeling in vascular morphogenesis); (4) the development of avascularity; (5) the differentiation of larger vessels from capillaries (histodifferentiation); (6) the role of growth factors in vascular and skeletal development. The goal is to understand the precursors, the pattern, and the permeability characteristics of the developing vascular system.