Ph.D Thesis

Ph.D StudentBresler Tal
SubjectThe Assembly of the Postsynaptic Element of Individual
Glutamatergic Synapses Formed between Hippocampal
DepartmentDepartment of Medicine
Supervisor PROF. Noam Ziv


Neurons communicate through specialized intercellular junctions known as synapses. Synapses are composed from presynaptic compartments which contain neurotransmitter filled vesicles and from postsynaptic compartments which are electron dense thickenings of the postsynaptic membranes that serve to confine neurotransmitter receptors and many additional molecules to the postsynaptic sites.

The major aim of this research project was to obtain insights on the cellular mechanisms of PSD assembly. Here we have employed (GFP) -tagged variants of four key PSD molecules, multisite time-lapse confocal microscopy, vital fluorescent labels and retrospective immunohistochemistry.

Our results suggest that new PSDs can form rather quickly, within an hour or less from axodendritic contact formation. All PSD molecules examined here were observed to be recruited to new postsynaptic sites in a gradual fashion, with no obvious involvement of large, discernable discrete transport particles, and with kinetics that could be described rather well by single exponential functions. The recruitment kinetics of all PSD molecules examined here were remarkably similar, which may indicate that PSD assembly rate is governed by a common upstream rate limiting process.  At preexisting PSDs, the same molecules displayed high rates of turnover/exchange with extrasynaptic pools, indicating that the PSD is a highly dynamic structure whose particular state is a net result of continuous molecule addition and loss. Taken together, our findings indicate that the formation of a new PSD is the end result of a rather rapid, spatially confined shift in the set point of PSD molecule addition and removal, most likely induced by a contact with a prospective axonal presynaptic partner.