Biography

William J. Schwartz received his M.D. (1974) and neurology residency training (1978-1981) at the University of California, San Francisco, completed a research fellowship at the National Institute of Mental Health (1975-1978), and was on the faculties of Harvard Medical School and the Massachusetts General Hospital (1981-1986) before moving to the University of Massachusetts. Visiting Professorships have included the Boerhaave Professor at Leiden University Medical Centre (2005) and the Baerends Visiting Chair at Rijksuniversiteit Groningen (2008), both in the Netherlands; and the Hood Fellow at the University of Auckland (2012), in New Zealand.

On the Neurobiology of Circadian Timekeeping

Daily rhythms of physiology and behavior are governed by an endogenous timekeeping mechanism (a circadian "clock"), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day-night cycle. Our knowledge of circadian timekeeping of animals at the molecular and cellular levels is remarkable, and laboratories here in the Department of Neurobiology are playing major roles in these advances (Emery, Reppert, Weaver). This laboratory is focused at the tissue, organismal, and even supra-organismal levels of analysis, and how all levels of biological organization contribute to the emergent properties and increased complexity of the circadian system as a whole.

Much of our work has focused on the suprachiasmatic nucleus (SCN) of the hypothalamus, the "master" circadian pacemaker of mammals, a tissue composed of multiple autonomous single-cell circadian oscillators (Figs 1 - 3). Our interests have included functional localization and energy metabolism, light-induced and endogenous gene expression, and the underyling dual oscillatory structure of the circadian pacemaker. We have been using molecular tools to show that some well-known circadian behaviors (e.g., "splitting," "forced desynchronization," and perhaps photoperiodism) emerge at the tissue level, in the dynamic interactions between SCN neurons rather than in the expression of "clock genes" within neurons.

For the most part, experiments on circadian rhythmicity (including our own) have been carried out using singly-housed animals in plastic cages with temperature, humidity, and access to food rigidly controlled. Of course, many species ordinarily would not live out their lives in such seclusion. They form real ecological communities, and some live in colonies with highly developed social structures and a clear division of labor, requiring modifications to daily rhythms. For other animals living in the wild, social factors might act to synchronize their behaviors to achieve common goals or, alternatively, actively avoid each other to lessen competition for limited resources. We have been asking if the circadian system is involved in the inter-individual temporal adaptations of cohabiting animals and what mechanisms might be responsible (e.g., whether social interactions alter the rhythmicity of animals with genetically-defective clocks, and the identification of the neurobiological substrates (molecules, cells, and pathways) that underlie circadian adaptation to complex habitats).

Figure 1. Coronal Nissl-stained section through the rat forebrain, including the bilaterally paired SCN (arrow).

Figure 2. Immunohistochemical arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) protein expression in a coronal section of the rat SCN, processed for double-label immunofluorescence and viewed using excitation wavelengths of 488 nm (green, for AVP) and 568 nm (red, for VIP).

Figure 3. The SCN exhibits endogenous day-night rhythms in energy metabolism, gene expression, and electrophysiological activity.