Bernardo L. Sabatini

Department of Neurobiology
Harvard Medical School
Goldenson Building, Room 316
220 Longwood Avenue, Boston, MA 02115

tel: (617) 432-5670; fax: (617) 734-7557
email: bernardo_sabatini@hms.harvard.edu

Research Interests

The acquisition of new behaviors and formation of memories occur through the creation and regulation of synaptic contacts within the brain. In mammals, most synapses form onto small, bulbous cellular compartments called dendritic spines. Spines are dynamic structures that appear rapidly following activity patterns that lead to memory formation and these fast structural alterations are believed to contribute to the remarkable plasticity of the brain. Each spine is biochemically isolated and contains components of many signaling pathways necessary for synaptic plasticity. One of the great challenges facing biology is the need to examine and manipulate biochemical pathways in situ where the natural distribution and movement of signaling components are preserved. In studying neurons, this problem is further compounded by the distributed nature of the cell. Cellular functions and organelles are scattered in disparate parts of the neuron and some compartments, such as dendrites and axons, are typically separated by hundreds of microns. Over short times, these compartments communicate only via electrical signals and, therefore, operate as largely independent biochemical compartments. Our inability to examine local intracellular signaling along with the small size of the relevant compartments are among the principal obstacles to understanding the intracellular pathways that control synaptic efficacy.

The goal for my laboratory is to study biochemical signaling within small cellular compartments such as dendritic spines in order to understand the pathways that trigger the formation of new synapses and the regulation of existing ones. We are combining molecular biology, electrophysiology, and microscopy to overcome some of the obstacles listed above. Of principal importance is the use of 2-photon laser scanning microscopy (2PLSM), which is ideally suited for measuring fluorescent signals from individual boutons or spines located within brain slices or in vivo. Our work builds on research I performed during graduate school and my postdoctoral fellowship in which we developed techniques to study calcium signaling in these compartments and uncovered regional specializations that underscored the need to study ion channel function and biochemical cascades in physiological settings.

 

Selected publications:

Sabatini, B. L., and Regehr, W. G. (1996). Timing of neurotransmission at fast synapses in the mammalian brain. Nature 384, 170-172.

Sabatini, B. L., and Svoboda, K. (2000). Analysis of calcium channels in single spines using optical fluctuation analysis. Nature 408, 589-593.

Sabatini, B. S., Oertner, T., and Svoboda, K. (2002). The life-cycle of Ca2+ ions in dendritic spines. Neuron 33, 439-452.

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