Electrophysiological description of mechanisms determining synaptic transmission and its modulation.

Signal integration in neurons is a complex process that depends on e.g. the kinetics of synaptic currents, distribution of synaptic connections as well as passive and excitatory membrane properties. The time course of synaptic currents is largely determined by the kinetics of the postsynaptic receptors and the time course of synaptic neurotransmitter concentration. The analysis of current responses to rapid agonist applications provides the means to study the ligand-gated receptor gating but experimentally based estimation of neurotransmitter transient at central synapses was an important challenge during the last decade. Both theoretical as well as experimentally based approaches indicated that synaptic agonist transient is very brief, implying that the activation of postsynaptic receptors occurs in conditions of extreme non-equilibrium. Such a dynamic pattern of activation of postsynaptic receptors has a crucial impact not only on the kinetics of synaptic currents but also on their susceptibility to pharmacological modulation.