Abstract
Variability in the size of single postsynaptic responses is a feature
of most central neurons, although the source of this variability
is not completely understood. The dominant source of variability
could be either intersynaptic or intrasynaptic. To quantitatively
examine this question, a biophysically realistic model of an idealized
central axospinous synapse was used to assess mechanisms underlying
synaptic variability measurements. Three independent sources of variability
were considered: stochasticity of postsynaptic receptors ("channel
noise"), variations of glutamate concentration in the synaptic cleft
(Deltaq), and differences in the potency of vesicles released from
different locations on the active zone release-location dependence
(RLD). As expected, channel noise was small (8\% of the total variance)
and Deltaq was the dominant source of variability (58\% of total
variance). Surprisingly, RLD accounted for a significant amount of
variability (36\%). Our simulations show that potency of release
sites decreased with a length constant of approximately 100 nm, and
that receptors were not activated by release events >300 nm away,
which is consistent with the observation that single active zones
are rarely >300 nm. RLD also predicts that the manner in which receptors
are added or removed from synapses can dramatically affect the nature
of the synaptic response, with increasing receptor density being
more efficient than merely increasing synaptic area. Saturation levels
and synaptic geometry were also important in determining the size
and shape of the distribution of amplitudes recorded at different
synapses.
- 12716926
- acid,
- ampa,
- biophysics,
- carlo
- computer
- excitatory
- glutamic
- gov't,
- method,
- models,
- monte
- n-methyl-d-aspartate,
- neurological,
- non-p.h.s.,
- non-u.s.
- of
- particle
- postsynaptic
- potentials,
- processes,
- receptors,
- reproducibility
- research
- results,
- simulation,
- size,
- stochastic
- support,
- synapses,
- synaptic
- transmission,
- u.s.
- vesicles,
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