|
Page 9 |
|
Profs. Spira and Bassell are using state-of-the art methodologies, including on-line confocal microscopy, to probe the molecular and cellular principles governing synapse formation and modification, which plays a crucial role in brain cell function in both health and disease.
Understanding how synapses are formed, maintained and modulated is of great importance. The prevailing hypothesis assumes they are formed via cascades of sequential signals generated by the participating neurons. By analogy to human behavior, this is like establishing a new friendship between two people. They first ask each other a series of questions and, if the answers are "right," a short- or long-term friendship gradually develops. In the parallel situation with two nerve cells, there is a series of signals, in response to which synapse structure and function is assembled step by step. Recent studies suggest an alternative faster process of synapse formation from pre-assembled cytoplasmic packets.
Cooperation Prof. Spira’s laboratory sent fixed nerve cell samples from Aplysia (a “sea snail” with a well-defined nervous system that has been used extensively to study the biophysics and molecular biology of learning and memory) to their United States collaborators. Prof. Bassel’s team used a fluorescent labeling method, developed in their laboratory, to visualize specific mRNA and protein molecules, using confocal microscopy. They also designed and constructed molecular probes, e.g., cDNAs and other probes, which were sent to Prof. Spira's laboratory for use in their experiments.
Findings Profs. Spira and Bassell focused on a third mode of synapse formation, in analogy with human behavior, which resembles "love at first sight." In this mode, neurons pre-fabricate the synaptic apparatus in advance in a "ready-to-go” form, in the absence of a synaptic partner. After “a short introduction,” during which the two nerve cells establish compatibility, a functional link (synapse) is rapidly established. This “strategy” seems to represent an “investment” of neuronal resources to enable fast synapse formation at a time when neurons are “competing” to establish synaptic contacts with post-synaptic partners. This slower restructuring of synaptic junctions comes into play in relation to learning and memory acquisition processes, during which neurons are already positioned within networks.
Varicosities or pre-assembled pre-synaptic terminal microtubules (red), actin (green) and vesicles (blue). This image was selected for inclusion in the permanent NeuroArt Exhibition, which opened in Barcelona in April 2006, prior to a world tour, to commemorate the 100th anniversary of the joint Nobel Prize awards to Santiago Ramón y Cajal and Camillo Golgi, for their contributions to the Neurosciences.
MAINTAINING CONTACTS BETWEEN NERVE CELLS
Prof. Noam Ziv: Department of Anatomy and Cell Biology, Technion-Israel Institute of Technology, Haifa
“This is our second BSF- funded project. Although our collaboration began before submitting our first BSF grant proposal, carrying out this work within the context of a joint grant was highly advantageous. While the financial support was very important, the fact that the projects were planned in detail and in advance, then peer-reviewed and finally approved, contributed greatly to the collaborative aspects and progress of our research.”
Prof. Craig Garner: Stanford University School of Medicine, Palo Alto, California
“Through these BSF grants, our laboratories have learned a great deal from each other, and have moved closer over these years, both intellectually and technologically. Also, the travel funds provided and used by students have been extremely instrumental in formulating direct and true collaborations between members of our laboratories, not requiring the constant involvement of the PIs.”
|
|
Confocal Microscope Image of Synapses |
