Reconstruction Data

Neurons

We labeled single neurons with biocytin to stain their axonal and dendritic morphologies to enable their 3D reconstruction and their objective classification into morphological types (m-types). In addition, we also characterized the electrical firing patterns of these neurons to different intensities of step currents injected in the soma to group their response into electrical types (e-types). We then mapped the e-types expressed in each m-type to account for the observed diversity of morpho-electrical subtypes (me-types)
Morphology-type

Neuron Morphology Generalization

Cloning
Axon grafting
Substitution
Due to lack of variety in neuron morphologies collected from extrapolated data, morphology reconstruction variants/clones are obtained by programmatically jittering branch angles and/or slightly modifying the length of segments.
Reconstructions are mainly performed on dendrites, there are only a few axons. To address this challenge, axons from one m-type are combined to the soma and dendrites of cells with the same morphology, as we assume they are compatible. This in turn generates new complete m-type models, increasing the diversity of neuron reconstructions.
Certain known m-types lack an extrapolated reconstruction morphology. In order to favour variability of cell types (as observed in vivo), the lacking m-type morphologies are substituted with other reconstructed models.
Morphology generalization illustration 1
Morphology generalization illustration 2
Morphology generalization illustration 3
Cloning
Due to lack of variety in neuron morphologies collected from extrapolated data, morphology reconstruction variants/clones are obtained by programmatically jittering branch angles and/or slightly modifying the length of segments.
Axon grafting
Reconstructions are mainly performed on dendrites, there are only a few axons. To address this challenge, axons from one m-type are combined to the soma and dendrites of cells with the same morphology, as we assume they are compatible. This in turn generates new complete m-type models, increasing the diversity of neuron reconstructions.
Substitution
Certain known m-types lack an extrapolated reconstruction morphology. In order to favour variability of cell types (as observed in vivo), the lacking m-type morphologies are substituted with other reconstructed models.
Electrophysiology-type

Neuron eletrophysiology generalization

Feature-based generalization
Although we have a large data set of experimental cell recordings, it is not feasible to record from every single neuron present in a circuit. Therefore, we pool the cells together in electrical types, and build a limited amount of models for each type. The constraints for each model are based on distributions of electrical features for each electrical type.
Neuron Electrophysiology generalization illustration
Ion channel generalization
Each neuron has a very diverse set of ion channels. There is no precise experimental data available showing which channels are present in each cell type, nor how the channels are distributed along the morphology. Therefore, we have selected channels based on literature, and let an optimization algorithm decide which channels are necessary for each firing type.
Neuron Electrophysiology generalization illustration
Threshold-based generalization
Even for the same firing and morphology type of neuron there are still significant differences between cells, for example in the size of the neurons. Since we don’t record from all of these differently sized cells, we normalize our protocols based on the firing threshold of the cells (rheobase). This way our neuronal model will generalize to morphologies of different sizes.
Neuron Electrophysiology generalization illustration
Morpho-electrophysiological-instance

Neuron morpholo-electrophysiological generalization

ME-Model generalization
Each of our models is built for one particular morphology. To make sure these models generalize to all morphologies in the circuit, we have a step called model management. During this step the protocols used for the parameter optimization are executed for each model using all the relevant morphologies. Each of these instances is scored based on how well they are still within range of the original experimental data. Morpho-electrical combinations that score badly are discarded and not used in the circuit.
Neuron Electrophysiology generalization illustration