CEREBELLAR GLOMERULI: DOES LIMITED EXTRACELLULAR CALCIUM DIRECT A
NEW KIND OF PLASTICITY?
O.J.-M. Coenen*; D.M. Eagleman; V. Mitsner; T.M. Bartol; A.J. Bell; T.J.
Computational Neurobiology Lab, Salk Institute, La Jolla, CA, USA
A class of synaptic learning models, in which a sum of
postsynaptic activity from many neurons drives plasticity, has generally
been considered biologically infeasible. After all, postsynaptic cell
bodies may be far apart, and there are no backward 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 (ECa). We propose the
theory that the ECa concentration in glomeruli may encode the level of
spike activity in postsynaptic cells. We investigate here cerebellar
glomeruli, where dendrites from 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 ECa will be proportional to the sum of granule
cell activity. We also show how these ECa 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. Although traditional neural
models emphasize only neurotransmitters and connectivity, these results
highlight the need to quantitatively address the 3D context in which axons
and dendrites are found.
Supported by: Sloan-Swartz, McDonnell-Pew, NIH, NSF, HHMI
Key words: CEREBELLUM, LEARNING, GLOMERULUS, GRANULE CELL
Click here for an MPEG movie of David Eagleman's Neural Growth simulator. (This movie may not work in Windows; try playing it on a Unix machine).
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.
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