Academic Background

B.A., Boston College
M.D., Harvard Medical School

Role of Intracellular Ca²⁺ Stores in Nerve Terminals and Exocytosis  

 The primary focus of this laboratory is on the role of intracellular Ca²⁺ stores in nerve terminals.   It is clear that Ca²⁺ influx from outside the terminal triggers exocytosis, and this process has been and continues to be the subject of intensive study.  In contrast the role of Ca²⁺ flowing into the cytosol of terminals from intracellular stores is unknown, and the very existence of such stores was in doubt until recently.  Using a preparation of freshly isolated nerve terminals from hypothalamic neurons, we have now demonstrated the existence of short-lived, focal, cyotosolic Ca²⁺transients arising from intraterminal stores.  In  certain respects these “Ca²⁺ sparks† found in myocytes, and hence we call these transients resemble “Ca²⁺ syntillas†from scintilla (L. spark) in a synaptic structure, a nerve terminal.  (DeCrescenzo et al, Journal of Neuroscience (2004) 24:1226-1235.)
 
The study of Ca²⁺ syntillas represents an entirely new field of presynaptic physiology, and we are presently examining the function and regulation of the syntillas and the nature of the stores from which they arise.  Our work on syntillas reflects both an interest in presynaptic function and in alterations in Ca²⁺ concentration within subcellular "microdomains." Ca²⁺ is a signal for an extraordinary number of cellular processes which presents the cell with the problem of undesirable cross-talk among the signaling pathways.  One way the cell avoids such cross-talk is to confine Ca²⁺ signals within microdomains. This we study by using widefield microscopy with high spatial and temporal resolution to follow Ca²⁺ changes in the cytosol and organelles of living cells with fluorescent Ca²⁺-sensitive dyes. We employ a unique digital imaging microscope which was developed by the Biomedical Imaging Group in our department in conjunction with Lincoln Laboratories at MIT. We believe this instrument, based on "Star Wars" technology, is the most powerful yet devised for this sort of study. More often than not we use imaging and patch clamping simultaneously.

A second and very recent interest of the laboratory is neurogenesis in the adult and the source and function of neural stem cells.

We work very closely with the Biomedical Imaging Group whose members include optical physicists, mathematicians and computer scientists.  These faculty members are a complement to the biologists and provide us with a highly talented set of collaborators, allowing us to use a genuine multidisciplinary approach.

Biomedical Imaging Group Home Page