Interneurons of the hippocampus

The cerebellum as a neuronal machine

In this paper a further study is made of the spontaneous synaptic potentials in frog muscle (Fatt & Katz, 1952a), and their relation to the end-plate response. It has been suggested that the end-plate potential (e.p.p.) at a single nerve-muscle junction is built up statistically of small all-or-none units which are identical in size with the spontaneous 'miniature e.p.p.'s'. The latter, therefore, could be regarded as the least unit, or the 'quantum', of end-plate response. A convenient picture of how hundreds of such quanta, each capable of producing a miniature potential of 0 5-1 0 mV, can build up an e.p.p. of, say, 70-80 mV is provided by the hypothesis that separate parcels of acetylcholine (ACh), released from discrete spots of the nerve endings, short-circuit the muscle membrane. The unit changes of membrane conductance produced at many parallel spots summate and lead to an intense depolarization of the muscle fibre. Although this is a plausible view, there is no direct proof that the normal e.p.p. is made up in this quantal fashion. The evidence comes from experiments in which the 'quantum content' of the e.p.p. had been reduced to a small number by lowering the external calcium concentration (Fatt & Katz, 1952 a). It was then found that the size of the end-plate response approached that of the spontaneous potential and at the same time exhibited large random fluctuations, apparently involving steps of unit size. Similar observations were made by Castillo & Engbaek (1954) on muscles treated with Mg-rich solutions. The statistical behaviour of the end-plate response under these conditions has been investigated in more detail and subjected to a quantitative analysis.

Quantal components of the end-plate potential

https://www.cell.com/cell/pdf/0092-8674(94)90556-8.pdf

Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse.

When brain tissue is homogenized in media iso-osmotic to plasma, the club-like presynaptic nerve endings resist disruption and are snapped or torn off from their attachments to form discrete particles (nerve-ending particles) in which all the main structural features of the nerve ending are preserved. For these particles we propose the name ' synaptosomes' in order to emphasize their relative homogeneity and their resemblance in physical properties to other subcellular organelles. They can be separated as a distinct fraction by differential and density-gradient centrifuging (Gray & Whit-Since acetylcholine is now well established, by all the classical criteria, as a central as well as a peripheral transmitter (for a review see Gaddum, 1961), it seems reasonable to conclude that the particle-bound acetylcholine and choline acetyltransferase of the fraction represent acetylcholine and enzyme localized within synaptosomes derived from chol-inergic neurones. Similarly, the 5-hydroxytrypt-amine and noradrenaline in this fraction are probably due to the presence of synaptosomes derived from neurones containing these amines. This view has been strengthened by the findings of Carlsson, Falck & Hillarp (1962), who have obtained histo-chemical evidence for the neuronal localization of these amines in the brain. The nerve endings and the synaptosomes derived from them have a complex fine structure when examined under the electron microscope with positive staining and thin sectioning (see review by Whittaker & Gray, 1962) or negative staining (Home & Whittaker, 1962). They are seen to consist (Plate 1 d) of thin-walled bags containing cytoplasm packed with synaptic granules or; frequently (though not in this example) one or more mitochondria are also present. The region of the post-synaptic membrane immediately adjacent to the ending is thickened; on homogenization it may remain adherent and accompany the synaptosome through the various steps of the fractionation procedure. Synaptic vesicles appear to be of at least three main kinds: 'hollow', 'dense-cored' and 'compound' (Plate 1 d). They have been proposed as the actual binding sites of transmitters within the nerve endings (De and as the morphological counterpart of the 'quantized' release of acetylcholine detected electrophysiologically (Fatt & Katz, 1952). The dense-cored vesicles are numerous in peripheral adrenergic nerve endings, and have there been proposed as the binding sites of noradrenaline. We have for some time been studying the disruption of synaptosomes with the object of obtaining , as separate fractions, synaptic vesicles, intraneuronal mitochondria, external and post-synaptic membranes and the soluble constituents of the nerve-ending cytoplasm for …

The separation of synaptic vesicles from nerve-ending particles (`synaptosomes')

The present study arose from the chance observation that end-plates of resting muscle fibres are the seat of spontaneous electric discharges which have the character of miniature end-plate potentials. The occurrence of spontaneous subthreshold activity at an apparently normal synapse is of some general interest, and a full description will be given here of observations which have been briefly reported elsewhere (Fatt & Katz, 1950a).

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1952.sp004735

P. Fatt

Papers

Spontaneous subthreshold activity at motor nerve endings