3D reverse engineering and simulation of signal flow in anatomically realistic neuronal networks

Marcel Oberlaender (Max Planck Florida Institute, Jupiter), Christiaan deKock (VU University Amsterdam), Randy Bruno (Columbia University, New York), Stefan Lang (IWR, Heidelberg), Bert Sakmann (Max Planck Florida Institute, Jupiter)

Soma location, dendrite morphology and presynaptic innervation represent key determinants of functional responses of individual neurons, such a sensory-evoked spiking. Here, we reverse engineer the three-dimensional networks formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify nine cell types and quantify the number and distribution of their somata, dendrites and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the three-dimensional soma location of the postsynaptic neuron. Our dataset provides the first three-dimensional anatomical description of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution. Simulation of signal flow, evoked by passive whisker touch, revealed that the three-dimensional structure of thalamocortical networks in a cortical column can account for cell type- and location-specific subthreshold and spiking responses. Thus, the present approach may allow investigating the cellular and subcellular mechanisms that underlie whisker-mediated behaviors.

3D reverse engineering and simulation of signal flow in anatomically realistic neuronal networks
a) Whisker-specific signals (such as touch) are conveyed by anatomically segregated pathways via the brainstem to the ventral posterior medial nucleus of the thalamus (VPM) and then to cortical barrel columns. b) The spatial organization of the barrel columns resembles the layout of the whisker pad on the animal’s snout. c) Input into a cortical barrel column is provided by excitatory neurons located in anatomically segregated, whisker-specific structures, called barreloids, in VPM. d) We illustrate the pipeline of reverse engineering and simulation of electrical activity on the example of an ensemble of L4 spiny stellate neurons that is activated by VPM input. e) 3D axon (blue) and dendrite (red) morphologies of individual neurons were reconstructed and assembled to an anatomically realistic network. f) In NeuroDUNE this network is converted into a numerical model, where L4 spiny stellate neurons are realized as full-compartmental models that receive input from spike generating VPM neuron models. Network connectivity (NC) is determined by structural overlap and functional measurements on convergence/divergence ratios.
Preferred presentation format: Poster
Topic: Computational neuroscience

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