Signaling in small subcellular volumes. II. Stochastic and diffusion
effects on synaptic network properties.
U. Bhalla. Biophys. J.87 (2):
The synaptic signaling network is capable of sophisticated cellular
computations. These include the ability to respond selectively to
different patterns of input, and to sustain changes in response over
long periods. The small volume of the synapse complicates the analysis
of signaling because the chemical environment is strongly affected
by diffusion and stochasticity. This study is based on an updated
version of a previously proposed synaptic signaling circuit (Bhalla
and Iyengar, 1999) and analyzes three network computation properties
in small volumes: bistability, thresholding, and pattern selectivity.
Simulations show that although there are diffusive regimes in which
bistability may persist, chemical noise at small volumes overwhelms
bistability. In the deterministic situation, the network exhibits
a sharp threshold for transition between lower and upper stable states.
This transition is broadened and individual runs partition between
lower and upper states, when stochasticity is considered. The third
network property, pattern selectivity, is severely degraded at synaptic
volumes. However, there are regimes in which a process similar to
stochastic resonance operates and amplifies pattern selectivity.
These results imply that simple scaling of signaling conditions to
femtoliter volumes is unlikely, and microenvironments, such as reaction
complex formation, may be essential for reliable small-volume signaling.