Estimating the electrotonic structure of neurons with compartmental models.

1. A procedure based on compartmental modeling called the "constrained inverse computation" was developed for estimating the electrotonic structure of neurons. With the constrained inverse computation, a set of N electrotonic parameters are estimated iteratively with use of a Newton-Raphson algorithm given values of N parameters that can be measured or estimated from experimental data. 2. The constrained inverse computation is illustrated by several applications to the basic example of a neuron represented as one cylinder coupled to a soma. The number of unknown parameters estimated was different (ranging from 2 to 6) when different sets of constraints were chosen. The unknowns were chosen from the following: dendritic membrane resistivity Rmd, soma membrane resistivity Rms, intracellular resistivity Ri, membrane capacity Cm, dendritic membrane area AD, soma membrane area As, electrotonic length L, and resistivity-free length, rfl (rfl = 2l/d1/2 where l and d are length and diameter of the cylinder). The values of the unknown parameters were estimated from the values of an equal number of known parameters, which were chosen from the following: the time constants and coefficients of a voltage transient tau 0, tau 1, ..., C0, C1, ..., voltage-clamp time constants tau vc1, tau vc2, ..., and input resistance RN. Note that initially, morphological data were treated as unknown, rather than known. 3. When complete morphology was not known, parameters from voltage and current transients, combined with the input resistance were not sufficient to completely specify the electrotonic structure of the neuron. For a neuron represented as a cylinder coupled to a soma, there were an infinite number of combinations of Rmd, Rms, Ri, Cm, AS, AD, and L that could be fitted to the same voltage and current transients and input resistance. 4. One reason for the nonuniqueness when complete morphology was not specified is that the Ri estimate is intrinsically bound to the morphology. Ri enters the inverse computation only in the calculation of the electrotonic length of a compartment. The electrotonic length of a compartment is l[4 Ri/(dRmd)]1/2, where l and d are the length and diameter of the compartment. Without complete morphology, the inverse computation cannot distinguish between a change in d or l and a change in Ri. Even when morphology is known, the accuracy of the Ri estimate obtained by any fitting procedure is affected by systematic errors in length and diameter measurements (i.e., tissue shrinkage); the Ri estimate is inversely proportional to the length measurement and proportional to the square root of the diameter measurement.(ABSTRACT TRUNCATED AT 400 WORDS)