Understanding the fundamental relationship between neuron structure
and function has long been an important goal in neuroscience. At all scales of
analysis, the roles that geometric shapes and spatial interrelationships play in
determining the functional abilities and constraints on brain activity are of
paramount consideration. Currently most modeling and simulations of the
electrical properties of neurons and their dendrites are carried out at a
relatively coarse scale, reflecting numerous simplifying assumptions about the
structure of dendrites. Such studies do not account for the small-scale
heterogeneity in dendritic structure and composition that are apparent at the
level of electron microscopy. Even our understanding of the electrical
differences between spiny and non-spiny dendrites may be incomplete due to an
over-reliance on simplified models.
The goal of this project is to bring together an interdisciplinary
collaboration comprised of computer scientists, mathematicians, and
neurobiologists to bring new reconstruction and computational tools to bear on
some of the most fundamental, outstanding questions in cellular
neuroscience. Specific goals
Constructing a scalable software framework for conducting multiscale
and spatially realistic electrical simulations of neuronal
Analyze how differences in head size, neck construction, surface
area, and intracellular organelles impact spine electrical
Investigate the role of active conductances both within spines and
along dendritic shafts and examine how heterogeneity in the distribution of ion
channels impacts dendritic signaling.
Scales of neuronal modeling. Black arrowheads indicate synaptic
input sites. Blue arrows indicate output sites. (a) Model of a neuron as a
single compartment. (b) Ball-and-stick neuron model represents dendritic
tree as long 1-D cable. (c) 1-D, branched
multi-compartment model of a CA1 pyramidal neuron with entire dendritic
tree (hundreds of microns long). (d) Realistic 3-D dendritic segment with
spines reconstructed from serial section electron microscopy (5-6 microns
long). (e) Cube of fully reconstructed neuropil (~6 microns on a side).
Axons in red; dendrites in gray.