Cooperative synapse formation in the neocortex

Abstract

IntroductionNeuron morphology plays an important role in defining synaptic connectivity. Clearly, only pairs of neurons with closely positioned axonal and dendritic branches can be synaptically coupled. For excitatory neurons in the cerebral cortex, such axo-dendritic oppositions, or potential synapses, must be bridged by dendritic spines to form synaptic connections. To explore the rules by which synaptic connections are formed within the constraints imposed by neuron morphology, we compared the distributions of the numbers of actual and potential synapses between pre-and post-synaptic neurons forming different laminar projections in rat barrel cortex. Quantitative comparison explicitly ruled out the hypothesis that individual synapses between neurons are formed independently of each other. Instead, the data are consistent with a cooperative scheme of synapse formation, where multiple-synaptic connections between neurons are stabilized, while neurons that do not establish a critical number of synapses are not likely to remain synaptically coupled.

Digital detection and analysis of branching and cell contacts in neural cell cultures

“…These estimates of potential nodes for single neurons agree surprisingly with those values reported from analysis of synaptogenesis based on detection by synaptic proteins labeling, see e.g. (Basarsky et al, 1994;McKellar and Shatz, 2009;Fares and Stepanyants, 2009). Therefore, the reliability of the proposed tool in extracting information about the potential synaptic density is verified.…”

“…An underlying assumption of the used synapse formation model is that actual synapses, for a given projection, are created at individual potential synaptic locations with a constant probability p. Hence, it was assumed that this probability is independent of synapse location on axonal and dendritic arbors, as well as its cortical position. Although, there are numerous examples of synaptic specificity within the potential connectivity matrix, it is thought that the above assumption holds for several neural networks in cultures as well (Fares and Stepanyants, 2009). Therefore, the model's concept is extended and it was possible to apply the model to the cases illustrated here.…”

“…where neuron pairs convert their individual potential synapses into actual synapses according to a fixed probability p. In Fares and Stepanyants (2009), it was discussed that the value of p depends on the type of cells under investigation and the region from which they were taken in the brain as well. Here we used a mean value of the reported values in the latter reference; then p is taken to be 0.2133 for all the next calculations.…”

“…The used model for estimating the actual synapses to be formed from the detected potential ones was first developed for a pair of cells with a certain degree of internal projection (Fares and Stepanyants, 2009). An underlying assumption of the used synapse formation model is that actual synapses, for a given projection, are created at individual potential synaptic locations with a constant probability p. Hence, it was assumed that this probability is independent of synapse location on axonal and dendritic arbors, as well as its cortical position.…”

“…The mere existence of a contact between a dendrite and an axon is a poor predictor of synapses, as several non-synaptic contacts occur per actual synapse (Fares and Stepanyants, 2009). Detection of actual synapses requires retrospective analysis using electron microscopy (EM), array tomography, direct imaging of synaptic proteins in vivo, or perhaps opto-physiological recordings with single synapse sensitivity.…”