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International audience; Synaptic plasticity is an extensively studied cellular correlate of learning and memory in which NMDARs play a starring role. One of the most interesting features of NMDARs is their ability to act as a co-incident detector. It is unique amongst neurotransmitter receptors in this respect. Co-incident detection is possible because the opening of NMDARs requires membrane depolarisation and the binding of glutamate. Opening of NMDARs also requires a co-agonist. Although the dynamic regulation of glutamate and membrane depolarization have been well studied in coincident detection, the role of the co-agonist site is unexplored. It turns out that non-neuronal glial cells, astrocytes, regulate co-agonist availability, giving them the ability to influence synaptic plasticity. The unique morphology and spatial arrangement of astrocytes at the synaptic level affords them the capacity to sample and integrate information originating from unrelated synapses, regardless of any pre-synaptic and post-synaptic commonality. As astrocytes are classically considered slow responders, their influence at the synapse is widely recognized as modulatory. The aim herein is to reconsider the potential of astrocytes to participate directly in ongoing synaptic NMDAR activity and co-incident detection.

The spatial organization of synaptic inputs on the dendritic tree of cortical neurons is considered to play an important role in the dendritic integration of synaptic activity. Active electrical properties of dendrites and mechanisms of dendritic integration have been studied for a long time. New technological developments are now enabling the characterization of the spatial organization of synaptic inputs on dendrites. However, quantitative methods for the analysis of such data are lacking. In order to place cluster parameters into the framework of dendritic integration and synaptic summation, these parameters need to be assessed rigorously in a quantitative manner. Here I present an approach for the analysis of synaptic input clusters on the dendritic tree that is based on combinatorial analysis of the likelihoods to observe specific input arrangements. This approach is superior to the commonly applied analysis of nearest neighbor distances between synaptic inputs comparing their distribution to simulations with random reshuffling or bootstrapping. First, the new approach yields exact likelihood values rather than approximate numbers obtained from simulations. Second and more importantly, the new approach identifies individual clusters and thereby allows to quantify and characterize individual cluster properties.

The spatial organization of synaptic inputs on the dendritic tree of cortical neurons plays a major role for dendritic integration and neural computations, yet, remarkably little is known about it. We mapped the spatial organization of glutamatergic synapses between layer 5 pyramidal cells by combining optogenetics and 2-photon calcium imaging in mouse neocortical slices. To mathematically characterize the organization of inputs we developed an approach based on combinatorial analysis of the likelihoods of specific synapse arrangements. We found that the synapses of intralaminar inputs form clusters on the basal dendrites of layer 5 pyramidal cells. These clusters contain 4 to 14 synapses within ≤30 µm of dendrite. According to the spatiotemporal characteristics of synaptic summation, these numbers suggest that there will be non-linear dendritic integration of synaptic inputs during synchronous activation. DOI: http://dx.doi.org/10.7554/eLife.09222.001, eLife digest Neurons in the brain exchange information through points of contact called synapses. If electrical activity arriving at a number of synapses exceeds a certain threshold, it can trigger an electrical impulse, which is transmitted to the next neuron. Synapses generally connect with branch-like structures called dendrites on the receiving neuron. However, little is known about how synapses are arranged on dendrites. Gökçe et al. have now used a technique called optogenetics to work out the exact arrangement of a type of synapse on neurons in a part of the mouse brain that is devoted to vision. Optogenetics takes advantage of light-activated proteins that can trigger electrical activity. Gökçe et al. used mice that had been genetically engineered to produce these proteins in specific neurons, and then deliberately triggered electrical activity simply by shining light on these neurons. The experiments also used another technique called two-photon calcium imaging to monitor the activity of single synapses in response to the electrical activity triggered by optogenetics. Gökçe et al. found that these neurons have clusters of four to fourteen synapses within a space of 30 micrometers along a dendrite. Synapses in clusters that are active at the same time can interact and thereby generate electrical signals more effectively than synapses spread across the dendrites. Further experiments are now needed to map the synapses between other kinds of neurons, and to map synapses from two different inputs at the same time. DOI: http://dx.doi.org/10.7554/eLife.09222.002