Quantitative morphometry of hippocampal pyramidal cells: differences between anatomical classes and reconstructing laboratories.

Abstract

The dendritic trees of hippocampal pyramidal cells play important roles in the establishment and regulation of network connectivity, synaptic plasticity, and firing dynamics. Several laboratories routinely reconstruct CA3 and CA1 dendrites to correlate their three-dimensional structure with biophysical, electrophysiological, and anatomical observables. To integrate and assess the consistency of the quantitative data available to the scientific community, we exhaustively analyzed 143 completely reconstructed neurons intracellularly filled and digitized in five different laboratories from 10 experimental conditions. Thirty morphometric parameters, including the most common neuroanatomical measurements, were extracted from all neurons. A consistent fraction of parameters (11 of 30) was significantly different between CA3 and CA1 cells. A considerably large number of parameters was also found that discriminated among neurons within the same morphological class, but reconstructed in different laboratories. These interlaboratory differences (8 of 30 parameters) far outweighed the differences between experimental conditions within a single lab, such as aging or preparation method (at most two significant parameters). The set of morphometrics separating anatomical regions and that separating reconstructing laboratories were almost entirely nonoverlapping. CA3 and CA1 neurons could be distinguished by global quantities such as branch order and Sholl distance. Differences among laboratories were largely due to local variables such as branch diameter and local bifurcation angles. Only one parameter (a ratio of branch diameters) separated both morphological classes and reconstructing laboratories. Compartmental simulations of electrophysiological activity showed that both differences between anatomical classes and reconstructing laboratories could dramatically affect the firing rate of these neurons under different experimental conditions.