Cerebellar Glomeruli: Does Limited
Extracellular Calcium
Direct a New Kind of Plasticity?
Olivier J.-M. D. Coenen;
David
M. Eagleman; Vladimir Mitsner;
Thomas M. Bartol; Anthony J. Bell; Terrence J. Sejnowski
CNL, The
Salk Institute for Biological Studies, La Jolla, CA, USA
| A class of synaptic learning models, in which a weighted sum of postsynaptic activity from many neurons drives plasticity, has generally been considered biologically infeasible. This rejection is not surprising under traditional notions of synaptic connectivity, since postsynaptic cell bodies may be far apart, and there are no backwards signals known to sum activity in a terminal-specific manner. However, some specialized synapses, known as glomeruli, become ensheathed by glial cells, and we suggest that these structures may allow for just such a postsynaptic summation. The ensheathment may force enclosed, neighboring dendrites to share a limited resource: extracellular calcium. We propose the theory that the instantaneous extracellular calcium concentration in glomeruli may encode the level of spike activity in postsynaptic cells. We investigate here cerebellar glomeruli, where dendrites from scores of granule cells swirl around a mossy fiber terminal, and the ensemble is tightly ensheathed in an astrocyte. Computer analyses of 3D simulated glomeruli, with realistic channel kinetics and Monte Carlo modeling of calcium diffusion using MCell indicate the range of conditions under which extracellular calcium will be proportional to the sum of granule cells activity. We also show how these extracellular calcium changes can be interpreted from an information-processing point of view, generating a novel learning rule for control of plasticity at the mossy fiber/granule cell synapse. This learning rule approaches a sparsely distributed and statistically independent coding in the parallel fibers. Both of these coding properties reduce the complexity of the credit assignment problem between active parallel fibers and the climbing fiber at a Purkinje cell. Although traditional neural models emphasize only neurotransmitters and point-to-point connectivity, these results highlight the need to quantitatively address the 3D biophysical context in which axons terminals and dendrites are found. |
D. M. Eagleman's Neural Growth
Simulator:
The simulator reproduces quantitatively the 3 dimensional geometry
of the cerebellar glomerulus as measured physiologically (Jakab, R.L. and
J. Hamori, 1988).
The following figure shows a snapshot of a Mcell
simulation, rendered with OpenDX,
with the astrocyte ensheatment (blue)
of the cerebellar glomerulus with a granule
cell dendrite (green) making contact with
the mossy fiber terminal (white) in the
center. The small
red dots near the dendrite
are calcium ions diffusing in the space
enclosed by the glial cell. The 3D structures within the glomerulus
were created by
the Neural Growth Simulator (see below). The figure was produced by
V. Mitsner.
The figure and MPEG movie below show, within a cerebellar glomerulus,
the growth of granule cell dendrites into the available space within the
glial ensheathment and the mossy fiber terminal. These figures and MPEG
movie were created by D. M. Eagleman.
For more information, please contact us about our upcoming manuscript: D. M. Eagleman, O. J-M. D. Coenen, T. Bartol, V. Mitsner, A. J. Bell, P. R. Montague, and T. J. Sejnowski, "Cerebellar glomeruli: Does limited extracellular calcium implement a sparse encoding strategy?", in preparation, 2001.