Search for: All records

Pyramidal neurons in neocortex have complex input-output relationships that depend on their morphologies, ion channel distributions, and the nature of their inputs, but which cannot be replicated by simple integrate-and-fire models. The impedance properties of their dendritic arbors, such as resonance and phase shift, shape neuronal responses to synaptic inputs and provide intraneuronal functional maps reflecting their intrinsic dynamics and excitability. Experimental studies of dendritic impedance have shown that neocortical pyramidal tract neurons exhibit distance-dependent changes in resonance and impedance phase with respect to the soma. We, therefore, investigated how well several biophysically detailed multicompartment models of neocortical layer 5 pyramidal tract neurons reproduce the location-dependent impedance profiles observed experimentally. Each model tested here exhibited location-dependent impedance profiles, but most captured either the observed impedance amplitude or phase, not both. The only model that captured features from both incorporates hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and a shunting current, such as that produced by Twik-related acid-sensitive K + (TASK) channels. TASK-like channel density in this model was proportional to local HCN channel density. We found that although this shunting current alone is insufficient to produce resonance or realistic phase response, it modulates all features of dendritic impedance, including resonance frequencies, resonance strength, synchronous frequencies, and total inductive phase. We also explored how the interaction of HCN channel current ( I h ) and a TASK-like shunting current shape synaptic potentials and produce degeneracy in dendritic impedance profiles, wherein different combinations of I h and shunting current can produce the same impedance profile. NEW & NOTEWORTHY We simulated chirp current stimulation in the apical dendrites of 5 biophysically detailed multicompartment models of neocortical pyramidal tract neurons and found that a combination of HCN channels and TASK-like channels produced the best fit to experimental measurements of dendritic impedance. We then explored how HCN and TASK-like channels can shape the dendritic impedance as well as the voltage response to synaptic currents. 

The approximately 100 billion neurons in our brain are responsible for everything we do and experience. Experiments aimed at discovering how these cells encode and process information generate vast amounts of data. These data span multiple scales, from interactions between individual molecules to coordinated waves of electrical activity that spread across the entire brain surface. To understand how the brain works, we must combine and make sense of these diverse types of information. Computational modeling provides one way of doing this. Using equations, we can calculate the chemical and electrical changes that take place in neurons. We can then build models of neurons and neural circuits that reproduce the patterns of activity seen in experiments. Exploring these models can provide insights into how the brain itself works. Several software tools are available to simulate neural circuits, but none provide an easy way of incorporating data that span different scales, from molecules to cells to networks. Moreover, most of the models require familiarity with computer programming. Dura-Bernal et al. have now developed a new software tool called NetPyNE, which allows users without programming expertise to build sophisticated models of brain circuits. It features a user-friendly interface for defining the properties of the model at molecular, cellular and circuit scales. It also provides an easy and automated method to identify the properties of the model that enable it to reproduce experimental data. Finally, NetPyNE makes it possible to run the model on supercomputers and offers a variety of ways to visualize and analyze the resulting output. Users can save the model and output in standardized formats, making them accessible to as many people as possible. Researchers in labs across the world have used NetPyNE to study different brain regions, phenomena and diseases. The software also features in courses that introduce students to neurobiology and computational modeling. NetPyNE can help to interpret isolated experimental findings, and also makes it easier to explore interactions between brain activity at different scales. This will enable researchers to decipher how the brain encodes and processes information, and ultimately could make it easier to understand and treat brain disorders.