Connectomic features underlying diverse synaptic connection strengths and subcellular computation

Abstract

SUMMARYConnectomes generated from electron microscopy images of neural tissue unveil the complex morphology of every neuron and the locations of every synapse interconnecting them. These wiring diagrams may also enable inference of synaptic and neuronal biophysics, such as the functional weights of synaptic connections, but this requires integration with physiological data to properly parameterize. Working with a stereotyped olfactory network in the Drosophila brain, we make direct comparisons of the anatomy and physiology of diverse neurons and synapses with subcellular and subthreshold resolution. We find that synapse density and location jointly predict the amplitude of the somatic postsynaptic potential evoked by a single presynaptic spike. Biophysical models fit to data predict that electrical compartmentalization allows axon and dendrite arbors to balance independent and interacting computations. These findings begin to fill the gap between connectivity maps and activity maps, which should enable new hypotheses about how network structure constrains network function.

Neural network organization for courtship-song feature detection in Drosophila

“…We tested this by predicting responses at each node in the connectome from the responses of the inputs using a simple linear model (Figure 6) and discovered strong predictability, suggesting that the wiring diagram places a strong constraint on functional responses, consistent with recent studies in the fly olfactory system. 50 Response continuums have been observed in fish 51,52 and rodents, [53][54][55] and are thought to support more efficient encoding than would be possible with categorical representations. In the fly auditory system, neurons with intermediate preference (that respond roughly equally to sine and pulse) could encode sound intensity, location, and/or long timescale features, such as the variable sequence of pulses and sines that make up song bouts.…”

Dendro-plexing single input spikes by multiple synaptic contacts enriches the computational capabilities of cortical neurons and reduces axonal wiring

“…Lastly, in recent years, multiple groups around the world have started to generate dense reconstruction of rodent and human neuronal (cortical) circuits at the EM level, and report neuronal connectivity maps 6,7,[66][67][68][69][70][71] . We would like to suggest that analyzing these EM datasets, focusing on the number of multiple contacts and their locations on the dendritic tree, might shed additional light on the extent and role of multiple synaptic contacts between different cell types and brain regions, and hint to the possible "style" of information processing in these networks based solely on EM data.…”

“…As illustrated in our work, if two neurons form a connection on distal dendrites, or if they form a connection on proximal dendrites, these will result in completely different time course of the somatic voltage and, therefore, on the temporal coding capabilities of the neuron. Indeed, simply reporting connectivity maps and even the size of post synaptic density (PSD) areas is not enough to determine the temporal influence of the connection on the post synaptic cell, as the dendritic location of the synapse is key, as was also shown by Rall 21,22 and recently also suggested in 69 . Furthermore, due to the nonlinear amplification of dendrites, such EM-based data will be crucial in assessing whether two presynaptic neurons connect to nearby dendritic locations as, in this case, these synapses are much more likely to undergo nonlinear amplification (and might produce additional broad/slow NMDA or calcium-dependent temporal filters) if activated at similar times.…”