A statistical analysis of dendritic morphology's effect on neuron electrophysiology of CA3 pyramidal cells
Introduction
In the CA3 subfield of the hippocampus, differences in pyramidal cell firing behavior, such as regular spiking versus complex spiking (or burst firing), may arise from differences in cell morphology. A relationship between cell morphology and neuron electrophysiology has been assumed since Ramon y Cajal theorized that cell variability may have a physiological effect [4]. Though the preponderance of literature focuses on complex spiking's dependence on the distribution of ionic channels [2], [3], [8], [16], [17], several studies have emphasized the existence and importance of the relationship between neuron morphology and neuron electrophysiology [1], [9], [10], [11], [12], [13], [14], [15], [18]. This relationship seems possible when looking at the anatomy of the CA3 region and the morphology of the cells within it. Bursting pyramidal cells are mainly found in the border regions of CA3a and CA3c, while pyramidal cells in the medial CA3b are spiking neurons [12]. It is possible that because cells within CA3c and other areas proximal to the dentate gyrus tend to have shorter dendritic trees while those in the distal portion of the CA3 have very long dendrites, the size of the dendritic trees may have a hand in determining if a cell exhibits complex spiking (bursts) or regular spiking [7].
Many of the research groups investigating neuron morphology's effect on neuron electrophysiology have compared neurons between different classes. Larkman and colleagues [10], [11] found that, of the three pyramidal cell classes they tested (neocortical layers 2, 3, and 5), only layer 5 pyramidal cells (having thick apical dendrites) showed bursting behavior. Mainen and Sejnowski [9] constructed computational models of neocortical spiny stellate, smooth stellate, and pyramidal cells (which had thicker dendritic trees than the other cell types in their sample), and showed that neocortical pyramidal cells (layers 2 and 3 to some degree, but layer 5 almost invariably) produced bursting behavior.
Other studies have focused on the effect of morphological differences within a single cell class. In one study using the Pinsky–Rinzel two-compartment pyramidal cell model, it was found that making the dendritic compartment appear distant from the soma, either by changing the coupling resistance between the two compartments or the membrane area ratio between the soma and dendrite compartments, the model changed from spiking to bursting behavior [14]. Although that study showed that morphological differences can have a qualitative effect on cell response, it did not statistically analyze the morphology of the cells’ dendrites.
The current study is a quantitative analysis of dendritic morphology's effect on neuron electrophysiology using computational models based on three-dimensional anatomical data of CA3 pyramidal neurons. We kept all physiological parameters (i.e., channel distributions and active conductances, membrane and axial resistances, and capacitances) constant across our cell sample. Using a set of morphometric parameters (parameters used to quantify three-dimensional morphological structure) we set out to determine how dendritic morphology was correlated with electrophysiological response (e.g., spike rate or burst rate). We also looked at which, if any, morphometric parameters determined qualitative differences in firing type for each cell.
Section snippets
Model
We constructed compartment models for each cell based on three-dimensional anatomical data. Neuroanatomical data concerning the dendritic structure of 16 CA3 pyramidal cells were obtained from the Southampton Archive [5], a collection of experimental morphological data. Four cells were obtained from CA3a, five from CA3b, four from CA3c, one from CA3-p/v, and one from CA2. The models of each of the 16 pyramidal cells were in the range of 1000–4000 compartments depending on the size of the cell's
Results and conclusions
Qualitative and quantitative responses of the sixteen cells to current injection varied greatly (see Fig. 2). Five cells exhibited only regular spiking, while another five exhibited bursting behavior, and six exhibited plateauing behavior. Since the channel distributions and the soma and axon sizes were kept homogenous across all cells, the only explanation for the difference in firing type was the difference in dendritic morphology.
There were numerous correlations between morphometric
Summary
The principal finding of this paper is that differences in the dendritic morphology of CA3 pyramidal cells have a significant effect on their electrophysiological response. Our results show that: (1) cells with smaller dendritic trees tend to be more excitable as measured by firing rate, (2) The change in diameter as a function of the branch distance from the soma as well as path length to the soma are indicators of firing behavior. The results presented in this paper constitute the first step of
Acknowledgements
This work was supported in part by Award No. 00-1 to G.A. Ascoli from the Commonwealth of Virginia's Alzheimer's and Related Diseased Research Award Fund, administered by the Virginia Center on Aging, Virginia Commonwealth University.
We would also like to acknowledge David E. Kirkpatrick for his assistance with some of the figures in this article.
Stuart D. Washington received his undergraduate degree in psychology from the George Washington University in 1998. Since that time, he has worked as a research assistant at the Krasnow Institute for Advanced Study at George Mason University. He is currently a Pre-Doctoral IRTA in the National Institute of Mental Health in the Laboratory of Neuropsychology. He is interested in biological and mathematical methods for comprehending the neural basis of cognition.
References (18)
- et al.
Variation in electrophysiology and morphology of hippocampal CA3 pyramidal cells
Brain Res.
(1990) - et al.
An on-line archive of reconstructed hippocampal neurons
J. Neurosci. Meth.
(1998) - et al.
Visual input evokes transient and strong shunting inhibition in visual cortical neurons
Nature
(1998) - et al.
An active membrane model of the cerebellar Purkinje cell I: Simulation of current clamps in slice
J. Neurophys.
(1994) Histology of Nervous System of Man and Vertibrates
(1995)- et al.
Endogenous nature of spontaneous bursting in hippocampal pyramidal neurons
Cell. Mol. Neurobiol.
(1981) - et al.
A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus
J. Comp. Neurol.
(1995) - et al.
A model for dendritic Ca2+ accumulation in hippocampal pyramidal neurons based on flourescence imaging measurements
J. Neurophys.
(1994) - et al.
Influence of dendritic structure on firing patterns in model neocortical neurons
Nature
(1996)
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Stuart D. Washington received his undergraduate degree in psychology from the George Washington University in 1998. Since that time, he has worked as a research assistant at the Krasnow Institute for Advanced Study at George Mason University. He is currently a Pre-Doctoral IRTA in the National Institute of Mental Health in the Laboratory of Neuropsychology. He is interested in biological and mathematical methods for comprehending the neural basis of cognition.
Giorgio A. Ascoli is a faculty member of the Krasnow Institute for Advanced Study and Visiting Assistant Professor in the Department of Psychology at George Mason University. He received his Ph.D. in biochemistry and neuroscience from the Scuola Normale Superiore of Pisa, Italy, and has a long-standing interest in the neurobiological basis of cognition. After several years of experimental work at the National Institutes of Health, Ascoli became interested in theoretical modeling and moved to Krasnow, where he leads the Computational Neuroanatomy Group.
Jeffrey L. Krichmar received a B.S. in Computer Science in 1983 from the University of Massachusetts at Amherst, a M.S. in Computer Science from The George Washington University in 1991, and a Ph.D. in Computational Sciences and Informatics from George Mason University in 1997. Currently, he is a Junior Fellow in Theoretical Neurobiology at The Neurosciences Institute in San Diego, CA. His research interests include biologically plausible models of learning and memory and simulating the nervous system in a real-world artifact (“robot”) interacting with an environment.