Dr. Siwek's lab is a component of a program project grant that is examining the effects of perinatal manipulation of dietary choline and folate. The work on this project (now entering its 11th year) is distributed among a number of different laboratories at BU, Duke University and VA Medical Centers in Bedford, MA and Durham, NC. The project has molecular biological, behavioral, nutritional, electrophysiological, genetic, and morphological components.

An important observation, made early in the projects history, is the fact that when the diet of pregnant mice is supplemented with choline in the chow and water, their offspring show a marked improvement in their performance in certain behavioral tasks (e.g. spatial memory). Because this effect is permanent, it suggests that there may be morphological changes that are associated with the improved behavioral performance.

As the neuroanatomical core for this project the work in Dr. Siwek's lab is examining the brains of these animals to try and identify morphological differences between control, choline supplemented and choline deficient groups. We are focusing our attention on the hippocampus and basal forebrain because of the critical role they play in learning and memory.

A powerful technique that has recently become more accessible is Unbiased Stereology. This method is used to make accurate estimates of size, number and volume in complex three-dimensional structures. In very simple terms, the method utilizes a systematic random sampling paradigm that means the objects of interest (neurons, plaques, glia etc) all have the same likelihood of being assessed and are not being subjected to human or methodological bias. By clearly delineating the boundaries of the structure or region being studied one can measure a known fraction of the total and use those measurements to compute an estimate that approaches the real value. Clearly in some cases, it is convenient to physically count or measure structures in total, but obviously there will be other cases where the counting or measuring is just too ponderous to undertake. That is where unbiased stereology becomes a powerful tool.

In addition to the choline research, Dr. Siwek has a long collaborative history with the Sleep Research Laboratory, directed by Dr. Subimal Datta. The primary concerns of this lab are the cellular and neurochemical mechanisms of REM sleep, the cellular basis of the brainstem PGO wave generation and the mechanisms underlying the cognitive functions of sleep. Work in this lab uses multidisciplinary techniques (Anatomy, Physiology, Pharmacology, Biochemistry, and Behavior) to study the basic mechanisms and functions of sleep. The specific goals of this work is to; 1. to understand how single cells of the brain and their specific chemical signals (neurotransmitters and neuromodulators) are organized at the level of population ensembles to determine the global behavioral states of waking and sleep; 2. to study the neurophysiological and molecular mechanism of state-dependent learning and memory consolidation; and 3. to study the consequences of altered brain development in the behavioral states of wake-sleep cycle. Dr. Datta received number of national and international awards for his contribution to the sleep research