Modeling the role of lateral membrane diffusion in AMPA
receptor trafficking along a spiny dendrite
AMPA receptor trafficking in dendritic spines is
emerging as a major postsynaptic mechanism for the expression of
plasticity at glutamatergic synapses. AMPA receptors within a spine
are in a continuous state of flux, being exchanged with local
intracellular pools via exo/endocytosis and with the surrounding
dendrite via lateral membrane diffusion. This suggests that one
cannot treat a single spine in isolation. Here we present a model of
AMPA receptor trafficking between multiple dendritic spines
distributed along the surface of a dendrite. Receptors undergo
lateral diffusion within the dendritic membrane, with each spine
acting as a spatially-localized trap where receptors can bind to
scaffolding proteins or be internalized through
endocytosis. Exocytosis of receptors occurs either at the soma or at
sites local to dendritic spines via constitutive recycling from intracellular pools. We derive a reaction--diffusion
equation for receptor trafficking that takes into account these
various processes. Solutions of this equation allow us to calculate
the distribution of synaptic receptor numbers across the population
of spines, and hence determine how lateral diffusion contributes to the
strength of a synapse. A number of specific results follow from our modeling and analysis. (i) Lateral membrane diffusion alone is insufficient as a mechanism for delivering AMPA receptors from the soma to distal dendrites. (ii) A source of surface receptors at the soma tends to generate an exponential--like distribution of receptors along the dendrite, which has implications for synaptic democracy. (iii) Diffusion mediates a heterosynaptic interaction between spines so that local changes in the constitutive recycling of AMPA receptors induce nonlocal changes in synaptic strength. On the other hand, structural changes in a spine following long term potentiation or depression have a purely local effect on synaptic strength. (iv) A global change in the rates of AMPA exo/endocytosis is unlikely to be the sole mechanism for homeostatic synaptic scaling. (v) The dynamics of AMPA receptor trafficking occurs on multiple timescales and varies according to spatial location along the dendrite. Understanding such dynamics is important when interpreting data from inactivation experiments that are used to infer the rate of relaxation to steady--state.
University of Utah
| Department of Mathematics
|
bressloff@math.utah.edu
Jan 2004.