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Patch pipettes were designed, initially, for the purpose of recording ionic currents through individual channels in cell membranes using a single pipette placed on a muscle membrane [28]. Here, we could watch a single biological molecule as it changed its structure by opening and closing a transmembrane pore. For example, at acetylcholine (ACh) concentrations of about 1 μM or higher, the same molecule switches repeatedly between an open and several closed state(s) [32]. The formation of a GΩ-seal between pipette tip and membrane widened the field of ion channel research. Currents were recorded with submillisecond resolution to resolve short opening and closing events [11]. Combined with genetic manipulation of ion channels expressed heterologously in Xenopus laevis oocytes, this technique facilitated the first structure–function assignments of ion channels. Single amino acids in putative pore-forming domains could be exchanged, and the subsequent effect on ion flows could be directly measured [20]. Finally, current recordings could be made from cell compartments such as the dendrite and terminal of a nerve cell. “Patch pipettes are, however, more useful than initially thought.” (Fred Sigworth) The whole-cell recording configuration also opened up a new field of research into the synapses of the mammalian central nervous system (CNS). In conjunction, the development of novel in vitro brain slice preparations and new visualization techniques in slices [12, 36] allowed us to characterize the properties of synapses in anatomically identified CNS pathways. Most useful were simultaneous whole-cell recordings made from cell pairs under visual control in combination with post hoc reconstructions of dendrites and axons of the two cells [26]. I will review the results we obtained by simultaneous pair recordings from preand postsynaptic CNS neurons and anatomical reconstructions. Each of the synapses we studied has a different function, and each is favorable to examine one particular aspect of synaptic function. One question relating to the properties of synapses in a neuronal network is how they might contribute to the magnitude and variability of AP responses observed in sensory systems. Unit recordings from single cells in sensory cortices indicate large differences both in the strength (efficacy) and trial-to-trial variability of suprathreshold responses. The contribution of synapses to this variability in particular is, so far, not well understood. By comparing three different synapses that are components of sensory pathways, we illustrate how one might be able to identify their contribution to the reliability of sensory representations. The rationale of this approach is to compare in vivo the magnitude and variability of response to sensory stimuli at different stages of a pathway. Concomitantly, a particular synapse between two stages is studied in vitro to delineate factors that determine synaptic efficacy and reliability. We first studied in vitro a relay synapse in the acoustic pathway. Cell pairs form an axosomatic synapse where the Pflugers Arch Eur J Physiol (2006) 453:249–259 DOI 10.1007/s00424-006-0172-4

Patch pipettes are more useful than initially thought: simultaneous pre- and postsynaptic recording from mammalian CNS synapses in vitro and in vivo