Estimating the number of release sites and probability of firing within the nerve terminal by statistical analysis of synaptic charge

Abstract

Investigating the function of individual synapses is essential to understanding the mechanisms that influence the efficacy of chemical synaptic transmission. The known simplicity of the synaptic structure at the crayfish neuromuscular junction (NMJ) and its quantal nature of release allows an assessment of discrete synapses within the motor nerve terminals. Our goal in this article is to investigate the effect of the stimulation frequency on the number of active release sites (n) and the probability of release (p) at those active sites. Because methods based on direct counts often provide unstable joint estimates of (n) and (p), we base our analysis on mixture modeling. In particular, the mixture modeling approach is used to estimate (n) and (p) for stimulation frequencies of 1 Hz, 2 Hz, and 3 Hz. Our results indicate that as the stimulation frequency increases, new sites are recruited (thus increasing n) and the probability of release (p) increases.

Actions of MDMA at glutamatergic neuromuscular junctions

“…Since multiple analysis protocols are utilized in the synaptic transmission field (Del Castillo and Katz, 1954;Cooper et al, 1995bCooper et al, , 1996Viele et al, 2003) to estimate the number of release sites and the probability of release, we provide the original values for further computational assessment by other investigators using their analysis protocol of choice.…”

Mixtures of Self-Modelling Regressions

“…Substantively, the finding of groups is expected, as such a finding can be directly linked to the underlying structural entities which are responsible for efficacy in chemical synaptic transmission in general [12,25,26]. However, if one fits a model with two groups, then two groups will appear in the results.…”

“…While we were able to adapt an existing information criterion for this assessment [19] and obtain reasonable results, in the future it will be important to formally develop an inferential procedure for MSIMs. Fortunately for the synaptic transmission data, simpler mixture models have also detected two groups [12].…”

“…This is our motivation for fitting a mixture of shape invariant functions, where the different underlying shape functions may indicate different active zones. Previous work in this area has uncovered groupings based on functionals of the traces, for example by fitting a normal mixture model on the peak amplitudes [12]. Of course, individual functionals only utilize a small amount of the information available in the entire voltage function.…”

Intrinsic differences in sensitivity to 5-HT between high- and low-output terminals innervating the same target

“…In addition, the standardized approach of obtaining n and p from methods of directly counting quantal events (del Castillo and Katz, 1954) and determining their distribution of occurrence underestimates the functional number of sites. For these reasons, we are beginning to develop novel statistical methods that incorporate differences in current sizes and shapes to estimate n and p (Viele et al, 2003). In the future it may be possible to revisit the data sets used in this current study to obtain better estimates of n and p to examine the influence of 5-HT on each parameter.…”