Synaptic Connectivity series Structure and function of ribbon synapses Peter Sterling 1 and Gary Matthews 2 1 Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA 2 Department of Neurobiology, State University of New York, Stony Brook, NY 11794, USA Sensory neurons with short conduction distances can use nonregenerative, graded potentials to modulate transmitter release continuously. This mechanism can transmit information at much higher rates than spiking. Graded signaling requires a synapse to sustain high rates of exocytosis for relatively long periods, and this capacity is the special virtue of ribbon synapses. Vesicles tethered to the ribbon provide a pool for sustained release that is typically fivefold greater than the docked pool available for fast release. The current article, which is part of the TINS Synaptic Connectivity series, reviews recent evidence for this fundamental computational strategy and its underlying cell biology. The synaptic ‘ribbon’ is an organelle expressed in the terminals of vertebrate photoreceptors and their second- order neurons (bipolar cells). Ribbons are also expressed by auditory and vestibular hair cells (reviewed in Ref. [1]) and in electrosensory receptors [2]. In fact, the ribbon seems to occur wherever synaptic exocytosis is evoked by graded depolarization and where signaling requires a high rate of sustained release (Figure 1). Ribbon synapses invariably use glutamate as the primary transmitter. The present article summarizes recent progress in understanding the role of this peculiar organelle (see also Refs [3–6]). Microscopic structure The photoreceptor ribbon is typically a plate, w30 nm thick, that extends perpendicular to the plasma mem- brane (Figures 2 and 3). The ribbon juts w200 nm into the cytoplasm, and never much more, but can vary in length from 200–1000 nm. The ribbon anchors along its base to an electron-dense structure (arciform density) that in turn anchors to the presynaptic membrane. This allows the ribbon to float w20 nm above the membrane like a flag or a balloon on a short leash. One puzzle is that hair cells lack an arciform density, so the anchor of the ribbon is invisible by standard electron-microscopic procedures. The ribbon’s surface is studded with small particles (w5 nm diameter) to which synaptic vesicles tether via fine filaments (w5 nm thick and w40 nm long). Usually there are several filaments per vesicle [7]. Tethered vesicles cluster densely but do not touch. Vesicles tethered along Figure 1. Diversity of ribbon synapses. (a) A hair cell. At the apical pole, cilia express the transduction channels. At the basal pole, ribbons (red; also known as ‘dense bodies’) tether numerous vesicles (white and yellow; the yellow vesicles are docked) near the presynaptic membrane. Each ribbon supplies one postsynaptic process. A hair cell typically contains 10–20 ribbons. (b) A cone terminal. Each ribbon (red) is located at the apex of an invagination that accommodates a triad of postsynaptic processes: two lateral processes (horizontal cells, H) and one central process (bipolar dendrite, B). Each cone typically expresses 20–50 triads. Flat contacts (FC) represent a different type of bipolar dendrite (Figure 5a). (c) A bipolar terminal. Each ribbon supplies a dyad of postsynaptic processes, which can comprise two ganglion cell dendrites (G), one ganglion cell dendrite and one amacrine process (A), or two amacrine processes. The amacrine processes often return a synapse to the bipolar terminal. Corresponding author: Sterling, P. (peter@retina.anatomy.upenn.edu). Available online 2 December 2004 Review TRENDS in Neurosciences Vol.28 No.1 January 2005 www.sciencedirect.com 0166-2236/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tins.2004.11.009