Computational convergence of the path integral for real dendritic morphologies

Neurons are characterised by a morphological structure unique amongst biological cells, the core of which is the dendritic tree. The vast number of dendritic geometries, combined with heterogeneous properties of the cell membrane, continue to challenge scientists in predicting neuronal input-output relationships, even in the case of sub-threshold dendritic currents. The Green’s function obtained for a given dendritic geometry provides this functional relationship for passive or quasi-active dendrites and can be constructed by a sum-over-trips approach based on a path integral formalism. In this paper, we introduce a number of efficient algorithms for realisation of the sum-over-trips framework and investigate the convergence of these algorithms on different dendritic geometries. We demonstrate that the convergence of the trip sampling methods strongly depends on dendritic morphology as well as the biophysical properties of the cell membrane. For real morphologies, the number of trips to guarantee a small convergence error might become very large and strongly affect computational efficiency. As an alternative, we introduce a highly-efficient matrix method which can be applied to arbitrary branching structures

Quantitative Analysis of Electrotonic Structure and Membrane Properties of NMDA-Activated Lamprey Spinal Neurons

Parameter optimization methods were used to quantitatively analyze frequency-domain-voltage-clamp data of NMDA-activated lamprey spinal neurons simultaneously over a wide range of membrane potentials. A neuronal cable model was used to explicitly take into account receptors located on the dendritic trees. The driving point membrane admittance was measured from the cell soma in response to a Fourier synthesized point voltage clamp stimulus. The data were fitted to an equivalent cable model consisting of a single lumped soma compartment coupled resistively to a series of equal dendritic compartments. The model contains voltage-dependent NMDA sensitive (INMDA), slow potassium (IK), and leakage (IL) currents. Both the passive cable properties and the voltage dependence of ion channel kinetics were estimated, including the electrotonic structure of the cell, the steady-state gating characteristics, and the time constants for particular voltage- and time-dependent ionic conductances. An alternate kinetic formulation was developed that consisted of steady-state values for the gating parameters and their time constants at half-activation values as well as slopes of these parameters at half-activation. This procedure allowed independent restrictions on the magnitude and slope of both the steady-state gating variable and its associated time constant. Quantitative estimates of the voltage-dependent membrane ion conductances and their kinetic parameters were used to solve the nonlinear equations describing dynamic responses. The model accurately predicts current clamp responses and is consistent with experimentally measured TTX-resistant NMDA-induced patterned activity. In summary, an analysis method is developed that provides a pragmatic approach to quantitatively describe a nonlinear neuronal system

Branching dendrites with resonant membrane: a “sum-over-trips” approach

Dendrites form the major components of neurons. They are complex branching structures that receive and process thousands of synaptic inputs from other neurons. It is well known that dendritic morphology plays an important role in the function of dendrites. Another important contribution to the response characteristics of a single neuron comes from the intrinsic resonant properties of dendritic membrane. In this paper we combine the effects of dendritic branching and resonant membrane dynamics by generalising the “sum-over-trips” approach (Abbott et al. in Biol Cybernetics 66, 49–60 1991). To illustrate how this formalism can shed light on the role of architecture and resonances in determining neuronal output we consider dual recording and reconstruction data from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in which an Ih current contributes to a voltage overshoot at the soma

Exact solutions to cable equations in branching neurons with tapering dendrites

Neurons are biological cells with uniquely complex dendritic morphologies that are not present in other cell types. Electrical signals in a neuron with branching dendrites can be studied by cable theory which provides a general mathematical modelling framework of spatio-temporal voltage dynamics. Typically such models need to be solved numerically unless the cell membrane is modelled either by passive or quasi-active dynamics, in which cases analytical solutions can be reduced to calculation of the Green's function describing the fundamental input-output relationship in a given morphology. Such analytically tractable models often assume individual dendritic segments to be cylinders. However, it is known that dendritic segments in many types of neurons taper, i.e. their radii decline from proximal to distal ends. Here we consider a generalised form of cable theory which takes into account both branching and tapering structures of dendritic trees. We demonstrate that analytical solutions can be found in compact algebraic forms in an arbitrary branching neuron with a class of tapering dendrites studied earlier in the context of single neuronal cables by Poznanski (Bull. Math. Biol. 53(3):457-467, 1991). We apply this extended framework to a number of simplified neuronal models and contrast their output dynamics in the presence of tapering versus cylindrical segments

Detecting and Estimating Signals in Noisy Cable Structures, II: Information Theoretical Analysis

This is the second in a series of articles that seek to recast classical single-neuron biophysics in information-theoretical terms. Classical cable theory focuses on analyzing the voltage or current attenuation of a synaptic signal as it propagates from its dendritic input location to the spike initiation zone. On the other hand, we are interested in analyzing the amount of information lost about the signal in this process due to the presence of various noise sources distributed throughout the neuronal membrane. We use a stochastic version of the linear one-dimensional cable equation to derive closed-form expressions for the second-order moments of the fluctuations of the membrane potential associated with different membrane current noise sources: thermal noise, noise due to the random opening and closing of sodium and potassium channels, and noise due to the presence of “spontaneous” synaptic input. We consider two different scenarios. In the signal estimation paradigm, the time course of the membrane potential at a location on the cable is used to reconstruct the detailed time course of a random, band-limited current injected some distance away. Estimation performance is characterized in terms of the coding fraction and the mutual information. In the signal detection paradigm, the membrane potential is used to determine whether a distant synaptic event occurred within a given observation interval. In the light of our analytical results, we speculate that the length of weakly active apical dendrites might be limited by the information loss due to the accumulated noise between distal synaptic input sites and the soma and that the presence of dendritic nonlinearities probably serves to increase dendritic information transfer

Fractional cable models for spiny neuronal dendrites

Cable equations with fractional order temporal operators are introduced to model electrotonic properties of spiny neuronal dendrites. These equations are derived from Nernst-Planck equations with fractional order operators to model the anomalous subdiffusion that arises from trapping properties of dendritic spines. The fractional cable models predict that postsynaptic potentials propagating along dendrites with larger spine densities can arrive at the soma faster and be sustained at higher levels over longer times. Calibration and validation of the models should provide new insight into the functional implications of altered neuronal spine densities, a hallmark of normal aging and many neurodegenerative disorders

High-order accurate difference schemes for the Hodgkin-Huxley equations

A novel approach for simulating potential propagation in neuronal branches with high accuracy is developed. The method relies on high-order accurate difference schemes using the Summation-By-Parts operators with weak boundary and interface conditions applied to the Hodgkin-Huxley equations. This work is the first demonstrating high accuracy for that equation. Several boundary conditions are considered including the non-standard one accounting for the soma presence, which is characterized by its own partial differential equation. Well-posedness for the continuous problem as well as stability of the discrete approximation is proved for all the boundary conditions. Gains in terms of CPU times are observed when high-order operators are used, demonstrating the advantage of the high-order schemes for simulating potential propagation in large neuronal trees