At present, there are no direct methods to determine the number of synaptic receptor-related channels activated in the course of synaptic transmission (N) or a value of the single-channel conductance (γ). Peak-scaled nonstationary fluctuation analysis (PS NSFA) should be considered the most well-developed indirect approach used for estimating these parameters. Despite the relatively wide using of this approach for the analysis of various synaptic currents, some aspects of possible errors that can occur in the course of data acquisition or their subsequent processing have not been studied. We examined in detail the problem of applicability of PS NSFA in the study of spontaneous and evoked GABA-ergic inhibitory postsynaptic currents (IPSCs). IPSCs were recorded using a dual patch-clamp technique from hippocampal neurons growing in low-density cultures. Parameters of the recorded IPSCs and values for different components of GABA-ergic synaptic transmission reported earlier were used for simulations and PS-NSFA analysis. In Monte Carlo computer simulations of evoked IPSCs, the influence of series resistance, background noise, asynchronicity of transmitter release, GABA A channel properties, dendritic attenuation, and instrumental filtering on γ estimates obtained by PS NSFA was examined. We concluded that the γ and, consequently, N values may be satisfactorily estimated by the suggested approach using spontaneous and evoked IPSCs recorded in inhibitory synaptic connections in hippocampal cultures within a wide range of experimental conditions. We also estimated the mean of the single-channel conductance of synaptic GABA A receptors in neurons from primary hippocampal cultures and found that this value (29 ± 5 pS) agrees well with the high conductance of single synaptic GABA A receptors observed in acute hippocampal slices. This indicates that dissociated cultures are an adequate model for studying the properties of synaptic GABA A receptors.

A most important component of the mammalian neocortex is the system of inhibitory interneurons. It is composed of cellular elements, which differ from each other in morphological, electrophysiological, and genetical features; these cells form a complex system of synaptic connections with glutamatergic cells and with each other. Some regularities that characterize the variety of types of cortical interneurons are discussed in our study.

Patterns of short-term synaptic plasticity could considerably differ between synapses of the same axon. This may lead to separation of synaptic receptors transmitting either low- or high-frequency signals and, therefore, may have functional consequences for the information transfer in the brain. Here, we estimated a degree of such separation at hippocampal GABAergic synapses using a use-dependent GABAA receptor antagonist, picrotoxin, to selectively suppress a pool of GABAA receptors monosynaptically activated during the low-frequency stimulation. The relative changes in postsynaptic responses evoked by the high-frequency stimulation before and after such block were used to estimate the contribution of this GABAA receptor pool to synaptic transmission at high frequencies. Using this approach, we have shown that IPSCs evoked by low-frequency (0.2 Hz) stimulation and asynchronous currents evoked by high-frequency (20-40 Hz) stimulation are mediated by different pools of postsynaptic GABAA receptors. Thus, our findings suggest that inhibition produced by a single hippocampal interneuron may be selectively routed to different postsynaptic targets depending on the presynaptic discharge frequency.