Graphical user interface (GUI).

A screenshot of the web-based GUI accessed via the Chrome browser. The interface is organized into three main components: the left menu, the main workspace, and the right menu. It supports both light and dark themes.

Dendritic morphology and segmentation.

(A) A schematic illustration of a neuronal morphology as three interconnected tree graphs. Colors indicate which morphological domains the nodes belong to. (B) Example of an L2/3 pyramidal neuron morphology from an SWC file. The selected section is highlighted in magenta. (C) Detailed representation of the selected section. Top: Diameter of the selected section as a function of the section’s length, with circles marking segment centers. Middle: Equivalent circuit of the selected section shown as an RC circuit, assuming a passive membrane. Bottom: Bar plot showing values of a user-selected parameter (surface area, µm2) for each segment. (D) Segmentation network graph representing the same cell as in (B) with d_lambda parameters of 0.2 (left) and 0.1 (right); nodes represent segments, colored as in (B). (E) Visualization of the selected morphological parameter on the segmentation graph using a color code. The lasso mouse tool is shown, which allows the selection of specific segments. Statistical morphometric analysis can be performed for the selected part of the cell. (F) Histogram of segment areas for basal (green) and apical (blue) segments.

Standardization of ion channel models.

(A) Schematic of parsing and standardizing ion channel models from MOD files. The converter automatically extracts the information from a MOD file via parsing and generates a Python file containing an IonChannel class. An instance of this class can be used to visualize channel kinetics. Standardization algorithm produces a StandardIonChannel class instance. The standardized channel model can then be exported to a new MOD file. (B) Kinetics of a voltage-gated sodium channel. Activation (purple) and inactivation (teal) curves for the steady-state value (top) and the time constant (bottom). The solid lines represent the original model, while the dashed lines depict the model with standardized equations fitted to the original curves. (C) Corresponding somatic voltage traces from the original model (solid) and one with both sodium and potassium channels standardized (dashed). Inset - the segment graph of the model. (D) Voltage traces for the same model (with standardized channels) constructed in DendroTweaks and simulated either in NEURON (solid) or in Jaxley (dashed).

Distributions of ion channels.

(A) Schematic showing a segment group in a ball-and-stick model, satisfying specific distance criteria. (B) Schematic showing distribution as a function of distance from the soma; values are assigned only to segments matching the group’s criteria. (C) Schematic showing the difference between domains and segment groups. A group can span multiple domains (left), match a single domain (middle), or partially include individual sections (right). (D) Example of a constant distribution for sodium channels, where maximal conductance in the selected region (dark blue) was decreased by 60%. Schematic electrodes indicate recording positions (inset: original morphology [Park et al., 2019]). (E) Example of an exponential distribution for the HCN channels (inset: original morphology [Poirazi et al., 2003]). (F) Example of a calcium ”hot spot” (red) (inset: original morphology [Hay et al., 2011]). (G) Sodium-driven backpropagation-activated action potentials (BAPs) evoked by a 0.162 nA somatic current injection. (H) Distribution of maximal HCN channel conductance as a function of distance from the soma (see functional effect in K). (I) Distribution of maximal calcium channel conductance as a function of distance from the soma (see functional effect in L). (J) Expanded time scale for the two scenarios in (D), showing failure of BAP initiation (blue arrow) in the region with reduced sodium conductance. (K) Voltage sag produced by HCN channels. A current step (-0.2 nA, 200 ms) is injected proximally (light cyan) and, after 300 ms, distally (dark cyan) in the apical trunk. Dashed traces: blocking HCN channels, modeled as 80% reduction in channel conductance. (L) Dendritic calcium plateau potential triggered by synaptic input at the calcium ”hot-spot” coincident with somatic current injection, leading to somatic bursting. Somatic traces are shown in orange, dendritic—in blue, cyan and gray.

Kinetics and distribution of synapses.

(A) Schematic representation of distributing synaptic inputs. Three central segments of a distal apical branch are selected using the lasso tool, and synapses are added (p—proximal, d—distal). (B) Example responses evoked by activating 20 excitatory synapses placed within one branch as in (A). The regularity of inputs varies from synchronous activation to a random Poisson spike train. Note that the raster plot for input times is accessible in one of the workspace tabs. The examples demonstrate dendritic voltage responses in the presence or absence of NMDA conductances. (C) Experiment similar to Doron et al., 2017 [Doron et al., 2017], demonstrating the effect of inhibiting NMDA spikes. Top: One inhibitory GABAA synapse is placed in the middle of the section, and its activation time varies as 0, 10, and 20 ms after excitatory synapse activation. Bottom: The synapse location varies from the most proximal to the most distal segment of the section, with the activation time kept at 20 ms. The same stimulation protocol as in (B) with synchronous activation is used for the excitatory inputs. Scale is the same as in (B). (D) Distributed placement of 40 excitatory AMPA-NMDA synapses across the dendritic tree, similar to Poirazi et al., 2003 (inset: original morphology). (E) Somatic and dendritic voltage responses to distributed synaptic inputs (D) (25 Hz, Poisson-distributed), which nearly fail to evoke somatic action potentials. Compare with (G) for clustered inputs. (F) Clustered placement of the same 40 excitatory synapses from (D) within five randomly selected branches. (G) Somatic and dendritic voltage responses to clustered synaptic inputs (F), demonstrating robust somatic firing activity. Somatic traces are shown in orange, dendritic - in blue and cyan.

Morphology reduction.

(A) Original morphology of L5 pyramidal neuron [Hay et al., 2011] and its segmentation graph showing the distribution of calcium channels. The red arrows indicate the ”hot-spots” with increased channel density. (B) Partially reduced morphology using the extended version of neuron_reduce. The extended version allows for the reduction of any selected branch, allowing to retain more apical branches, in contrast to (C). (C) Fully reduced morphology. All stem dendrites (children of the soma) are reduced to a single equivalent cylinder. (D-F) Voltage response of the three models to somatic current injection of 0.5 nA. Note the difference in the number of dendritic ”hot-spots” and somatic APs between the three variations of the model. The partially reduced model more accurately reproduces the channel distribution and voltage response of the original model compared to the fully reduced one.

Validation protocols

Validation protocols.

Built-in validation protocols applied to the Hay et al., 2011 model [Hay et al., 2011]; See also Table 1). (A) Membrane time constant (34 ms) measured by applying a step current injection (-0.05 nA) at the soma, while blocking the HCN channels. (B) Voltage attenuation for somatic (-0.5 nA, left) and dendritic (-0.05 nA, right) step current injection at all bifurcation points along the path from a selected tip segment. (C) Detected somatic action potentials from stimulation with a positive step current (0.793 nA). (D) Single action potential indicated with an arrow in (C), with measured peak, amplitude, and half-width values. (E) Somatic frequency-current (f-I) curve constructed by applying current steps of increasing amplitude (0.1 nA step) at the soma. (F) Nonlinear integration of synaptic inputs in a tuft dendrite. Left: Expected vs. actual EPSP amplitude for 1 to 60 synchronously activated AMPA-NMDA synapses. Right: Actual EPSP waveforms. (G) Voltage sag ratio at the soma measured by applying a negative step current injection (-0.05 nA). Note that unlike in (A), the hyperpolarization-activated current through the HCN channels is present here.