Abstract The use of advanced patch-clamp recording techniques in brain slices, such as simultaneous record- ing from multiple neurons and recording from dendrites or presynaptic terminals, demands slices of the highest quality. In this context the mechanics of the tissue slicer are an important factor. Ideally, a tissue slicer should generate large-amplitude and high-frequency move- ments of the cutting blade in a horizontal axis, with minimal vibrations in the vertical axis. We developed a vibroslicer that fulfils these in part conflicting require- ments. The oscillator is a permanent-magnet-coil-leaf- spring system. Using an auto-resonant mechano-electri- cal feedback circuit, large horizontal oscillations (up to 3 mm peak-to-peak) with high frequency (≈90 Hz) are generated. To minimize vertical vibrations, an adjust- ment mechanism was employed that allowed alignment of the cutting edge of the blade with the major axis of the oscillation. A vibroprobe device was used to moni- tor vertical vibrations during adjustment. The system is based on the shading of the light path between a light- emitting diode (LED) and a photodiode. Vibroprobe monitoring revealed that the vibroslicer, after appropri- ate adjustment, generated vertical vibrations of <1 μm, significantly less than many commercial tissue slicers. Light- and electron-microscopic analysis of surface lay- ers of slices cut with the vibroslicer showed that cellular elements, dendritic processes and presynaptic terminals are well preserved under these conditions, as required for patch-clamp recording from these structures. Keywords Adjustable vibroslicer · Auto-resonant mech- ano-electrical feedback circuit · Vibroprobe · Brain slices · Paired recordings · Dendrites · Presynaptic terminals · Hippocampal mossy fibre boutons Introduction Patch-clamp recording from neurons has advanced our understanding of electrical and chemical signalling in the mammalian central nervous system substantially. Land- marks of technical improvement were the application of patch-clamp techniques to neurons in brain slices [2, 5], the combination with infrared differential interference contrast (IR-DIC) videomicroscopy [4, 13, 19, 21], the recording from pairs of synaptically connected neurons [9, 12, 14, 16] and the recording from small subcellular structures, such as dendrites and presynaptic elements [3, 6, 8, 15, 19, 20, 21]. For both paired recording and re- cording from subcellular structures, the quality of the slice preparation is of eminent importance. When record- ings are made under the visual control provided by IR- DIC [19, 21], the integrity of the superficial layers of the slice is a particularly relevant issue. As structures are ap- proached typically with positive pressure in the patch pi- pette without “cleaning” [19, 21], recording is restricted to a region 10–100 μm below the surface of the slice. Unfortunately, however, the preservation of the superfi- cial layers is often poor with conventional slicing tech- niques [7, 17]. Several factors are thought to affect slice quality. First, solutions used for cutting and storage are impor- tant. For example, addition of ascorbic acid [3, 18] or pyruvate [3, 6] and replacement of NaCl by sucrose [8] are thought to be advantageous for the preservation of the tissue. Second, the properties of the tissue slicer used for cutting are important. Experience shows that three aspects are of primary relevance: (1) the amplitude of the horizontal oscillation has to be sufficiently large, espe- cially for brain regions with a high abundance of myelin- ated fibres (such as spinal cord or brainstem); (2) the fre- J.R.P. Geiger · J. Bischofberger · U. Fröbe · S. Pfitzinger H.J. Weber · K. Haverkampf · P. Jonas ( ✉ ) Physiologisches Institut der Universität Freiburg, Abteilung I, Hermann-Herder-Strasse 7, 79104 Freiburg, Germany e-mail: jonasp@uni-freiburg.de Tel.: +49-761-2035150, Fax: +49-761-2035204 I. Vida Anatomisches Institut der Universität Freiburg, Abteilung I, Albertstrasse 17, 79104 Freiburg, Germany Pflügers Arch - Eur J Physiol (2002) 443:491–501 DOI 10.1007/s00424-001-0735-3 INSTRUMENTS AND TECHNIQUES J. R. P. Geiger · J. Bischofberger · I. Vida · U. Fröbe S. Pfitzinger · H. J. Weber · K. Haverkampf · P. Jonas Patch-clamp recording in brain slices with improved slicer technology Received: 4 May 2001 / Revised: 1 June 2001 / Accepted: 12 September 2001 / Published online: 17 October 2001 © Springer-Verlag 2001