23. Binomial analysis accounting for functional differences between neocortical synaptic connections

Antoine Bremaud antoine.bremaud@pharmacy.ac.uk Alex Thomson

Department of Pharmacology, School of Pharmacy, London, UK

The simple binomial model of synaptic release considers a connection as made of a number of release sites (n), each with an identical, but independent probability (p) of releasing transmitter upon spike arrival, resulting either in a failure of transmission, or a quantal postsynaptic response (q) (del Castillo and Katz, 1954). This model predicts specific relationships between the statistics of the resulting postsynaptic response amplitudes.

Synaptic connections were studied using dual sharp microelectrode recordings in slices of adult rat and cat neocortex and recorded cells filled with biocytin. Current injections elicited trains of action potentials in the presynaptic cell and excitatory postsynaptic potentials (EPSPs) were recorded in the postsynaptic cell. By varying the amplitude and shape of the injected current, a range of presynaptic firing patterns was elicited, allowing the statistics and dynamics of the EPSP amplitude fluctuations to be studied.

When connections involving different classes of neurones were compared, inherent differences in the relationships linking their statistics of release were revealed (Bremaud et al., 2007). Most strikingly, the variability in amplitude for a given mean EPSP amplitude differed.

To explore these differences further, methods exploiting the statistical relations predicted by the simple binomial model were employed and the binomial parameters n, p and q estimated. Significant differences between these parameter estimates were found when different classes of connection were compared.

The simple binomial model assumes uniform p and q across all n release sites (at any one time). To determine whether our analysis would be meaningful if more complex schemes were to underlie release, Monte Carlo simulations of models in which p and q varied across release sites were also run.

More complex models could generate significant shifts in parameter estimates, but the scale of these shifts was smaller than the experimentally obtained differences between connection classes. The parameters obtained were concluded to be acceptable estimates of n, mean p and mean q, and to demonstrate that each connection class employs a different combination of these parameters to achieve a given synaptic strength.

Bremaud, A., West, D. C., & Thomson, A. M. (2007) Binomial parameters differ across neocortical layers and with different classes of connections in adult rat and cat neocortex. Proc. Natl. Acad. Sci. U. S. A 104, 14134-14139.
del Castillo, J. & Katz, B. (1954) Quantal components of the end-plate potential. J. Physiol 124, 560-573.