Sensory end-organs: signal processing in the periphery: a symposium presented at the 2013 Annual Meeting of the Society for Neuroscience, San Diego, CA, USA.

Abstract

From November 9 to 13, 2013, over 30,000 neurobiologists travelled to San Diego, California to attend the Annual Meeting of the Society for Neuroscience (SFN2013). At this conference on Tuesday morning, November 12, The Journal of Physiology and the Physiological Society sponsored a symposium entitled Sensory end-organs: signal processing in the periphery, chaired by one of The Journal's editors, S. Roper. The symposium featured several distinguished speakers who presented up-to-the-minute findings on different peripheral sensory structures (Fig.​(Fig.1).1). Nirupa Chaudhari described recent findings in gustation and how taste buds process gustatory signals (Chaudhari, 2014). Paul Fuchs reported on auditory processing in the cochlea, focusing on efferent control of outer hair cells (Fuchs, 2014). Susan Carlton discussed pain and modulation of peripheral nociceptors by a number of influences, including retrograde efferent activation of terminals (Carlton, 2014). Alejandro Caicedo presented evidence for local paracrine and autocrine control of glucose sensing in pancreatic islets of Langerhans (Rodriguez-Dias et al. 2014). Colin Nurse, although unable to attend and present, was a symposium contributor. His presentation on synaptic interactions in the carotid body is included in the present overview of the symposium (Nurse, 2014). The common theme of the speakers was that sensory end-organs are not passive receptors that merely respond reflexively to external stimuli. Instead, a significant amount of signal processing takes place in peripheral sensory receptors and organs. Sensory signals are modulated, smoothed, amplified and otherwise shaped in the periphery prior to being transmitted to the central nervous system. Efferent modulation as well as local interactions between cells within sensory organs significantly modify the signals that are transmitted to the brain. Efferent neurotransmitters and paracrine secretions, including serotonin, ACh, glutamate, GABA and ATP, act as modulators during sensory signalling. Figure 1 Featured sensory end-organs Signal processing in peripheral receptor organs challenges the concept of ‘labelled line sensory coding’. Although labelled line coding for some senses, such as olfaction, has never been seriously considered, the notion that certain sensations are communicated by single axons, or ‘lines’ is hotly debated in other senses and is promulgated in major textbooks. The origin of the concept of labelled line coding might be traced as far back as Descartes (1680). That is, the text accompanying his oddly cherubic drawing depicting painful heat (from flames) being transmitted to the brain (Fig.​(Fig.2)2) describes that ‘particles of the fire’ act by ‘…pulling the little thread [and] simultaneously open the entrance to the pore … where this thread terminates [in the brain]’ (Hall, 1972). Vis-a-vis labelled line coding, the ‘label’ is painful heat. The ‘line’ is the thread. Figure 2 Nociception, as explained by Rene Descartes in 1680 However, the birth of labelled line sensory coding is generally credited to the great 19th century anatomist and physiologist, Johannes Muller. Muller postulated that sensory end-organs and their connections to the brain, not the nature of the external stimulus per se, dictates each specific perception (Muller, 1834). Thus, mechanical perturbation of touch receptors in the skin generates the sensation of a tap, but a similar mechanical stimulation (if strong enough) applied to the eye generates flashes of light. The receptor and its fibre connections (the ‘line’) dictate the perception (the ‘label’). Although he himself did not coin the phrase, this principle has come to be known as Muller's Law of Specific Nerve Energies (LOSNE). To be fair, the Scottish surgeon, Charles Bell (1811) had previewed this concept somewhat earlier in a pamphlet he published and circulated privately, as discussed by Norrsell et al. (1999). Experimental tests of the principle of Specific Nerve Energies were carried out by electrically stimulating cutaneous nerves (‘lines’) with focal external electrodes to elicit specific sensations (‘labels’) of touch, first by the Swedish physiologist Magnus Blix in 1882 (reviewed in Norrsell et al. 1999) and much later by microelectrode penetrations into superficial nerves, microneurography (Vallbo & Hagbarth, 1968). The early progression of ideas behind labelled line coding (or LOSNE), particularly for somatosensory stimuli, from Johannes Muller through Charles Bell, Magnus Blix, Max von Frey, Jerzy Edwin Rose and Vernon Mountcastle, is colourfully described (and sometimes attacked) in a number of excellent reviews, including Weddell (1955), Sinclair (1955), Melzack & Wall (1962) and Norrsell et al. (1999). Labelled line coding has also been claimed for taste by some researchers (Gordon et al. 1959; Hellekant et al. 1998; Yarmolinsky et al. 2009). These claims are based largely on electrophysiological recordings from single gustatory nerve fibres or from functional imaging and molecular characterizations of taste bud cells. In experiments using electrical stimulation of the tongue in human subjects, reminiscent of the much earlier work by Magnus Blix, von Bekesy (1964) excited individual taste buds with fine-tipped electrodes. Such stimulation selectively evoked sensations of sweet, sour, salty or bitter taste, perhaps consistent with the notion of labelled lines. Yet early developments in vision research led to a very different view of sensory coding. In his Bakerian Lecture, Thomas Young (1802) proposed that ‘particles’ in the retina (retinal ganglion cells?) sense colours by combining three principal hues – red, yellow and blue. To his credit, Young cites allusions to this idea by Isaac Newton and quotes Newton's colourful explanation of light as ‘vibrations in the ether, which … cause a sensation of light by beating and dashing against the bottom of the eye’. Later, Helmholz further developed Young's ideas and put them on solid physiological underpinnings in his masterful treatise on optics (Helmholtz, 1911). The point is that colour vision has long been recognized as combinatorial coding of multiple receptors, not as labelled lines for all the different perceived hues. Somatosensory responses also have been viewed as some form of combinatorial, or more accurately, pattern coding (Nafe, 1927; Sinclair, 1955; Weddell, 1955). These authors conclude that information is not encoded in any single sensory afferent but ‘that what leaves the skin as a result of cutaneous stimulation is a complex spatially and temporally dispersed pattern of impulses…’ (Sinclair, 1955). Melzack & Wall (1962) co-authored a scholarly appraisal and refinement of impulse pattern coding. Similarly, olfaction was long ago surmised to involve some form of spatiotemporal code in the olfactory epithelium or olfactory bulb, or both (Adrian, 1953). The detailed molecular combinatorial coding for olfaction at the receptor cell level was solved by L. Buck and colleagues (Malnic et al. 1999). Coding for odours in the olfactory bulb is still a lively topic of current investigation and is likely to involve spatial, temporal and pattern coding (Zou et al. 2009; Gire et al. 2013). Finally, patterned or combinatorial coding of sensory afferents in gustation has been and today still remains a more likely explanation of how taste information is encoded in transit from the peripheral end-organs (taste buds) into the brain. A population of individual gustatory receptor cells in taste buds is relatively specific for each of the different taste qualities (sweet, bitter, umami; Tomchik et al. 2007). However, cell–cell synaptic interactions in taste buds appear to shape the output signals (Tomchik et al. 2007; Chaudhari & Roper, 2010; Roper, 2013; Chaudhari, 2014). Moreover, it has long been known that individual gustatory afferent neurons have at best a preferred stimulus (e.g. ‘sweet-best’ or bitter-best’), not an exclusive, absolute ‘label’ (Frank, 1973). Indeed, some gustatory afferent neurons are broadly responsive to many taste qualities and support the contention of a patterned code for taste (Pfaffmann, 1941; Erickson, 1963; Lundy & Contreras, 1999; Sollars & Hill, 2005). The historical development and analysis of taste coding is nicely reviewed in Smith & Frank (1993), Spector & Travers (2005), Erickson (2008) and Chaudhari & Roper (2010). In summary, efferent modulation of peripheral sensory cells and cell–cell communication in sensory end-organs strongly indicate that sensory signalling is far more complex than can be accounted for by any simple labelled line coding and is more consistent with combinatorial or patterned coding. Sensory signals can be enhanced, suppressed, mixed and otherwise shaped by the processes that were discussed in the SFN2013 symposium.