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Cerebral Cortex Advance Access first published online on April 27, 2005
This version published online on June 9, 2005
Cerebral Cortex, doi:10.1093/cercor/bhi086
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Article

Growth of Neurites toward Neurite-Neurite Contact Sites Increases Synaptic Clustering and Secretion and Is Regulated by Synaptic Activity

Joshua Cove 1 *, Pablo Blinder 1 *, Elia Abi-Jaoude 2 *, Myriam Lafrenière-Roula 3, Luc Devroye 4, and Danny Baranes 1*

1 Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; Zlotowsky Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
2 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8
3 Spinal Cord Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3J7
4 School of Computer Science, McGill University, Montreal, Canada H3A 2K6

* To whom correspondence should be addressed.
Danny Baranes, E-mail: dbaranes{at}bgumail.bgu.ac.il


  Abstract

The integrative properties of dendrites are determined by several factors, including their morphology and the spatio-temporal patterning of their synaptic inputs. One of the great challenges is to discover the interdependency of these two factors and the mechanisms which sculpt dendrites' fine morphological details. We found a novel form of neurite growth behavior in neuronal cultures of the hippocampus and cortex, when axons and dendrites grew directly toward neurite-neurite contact sites and crossed them, forming multi-neurite intersections (MNIs). MNIs were found at a frequency higher than obtained by computer simulations of randomly distributed dendrites, involved many of the dendrites and were stable for days. They were formed specifically by neurites originating from different neurons and were extremely rare among neurites of individual neurons or among astrocytic processes. Axonal terminals were clustered at MNIs and exhibited higher synaptophysin content and release capability than in those located elsewhere. MNI formation, as well as enhancement of axonal terminal clustering and secretion at MNIs, was disrupted by inhibitors of synaptic activity. Thus, convergence of axons and dendrites to form MNIs is a non-random activity-regulated wiring behavior which shapes dendritic trees and affects the location, clustering level and strength of their presynaptic inputs.

Keywords: dendritic morphology; neurite-neurite contact; synaptic clustering; synaptic secretion.

*These authors contributed equally to this work.

CNQX and TTX have been corrected on pages 6, 8 and in Figure 6.


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