- Email: [email protected]
Sensory systems
437
Sensory systems Editorial overview David P Corey’ and Charles S Zuker* Addresses ‘Howard Hughes Medical Institute and Department of Neurobiology, Wellman 414, Massachusetts General Hospital, Boston, Massachusetts 02114, USA, e-mail: [email protected] 2Howard Hughes Medical Institute and Departments of Biology and Neuroscience, University of California at San Diego, La Jolla, California 92093, USA; e-mail: [email protected] Abbreviation PDE cGMP-phosphodiesterase
Current Opinion in Neurobiology 1996, 6:437-439 0 Current Biology Ltd ISSN 0959-4388
Introduction The study of sensory systems dates back several centuries, beginning with primitive, descriptive studies of pain sensation, extending to current sophisticated experiments that analyze the coding of sensory information in the CNS. The past few years have witnessed a tremendous progress in the field, fueled by advances in technology combined with new insights into the cellular and molecular biology of sensory receptor cells. For this issue of Current Opinion in Neurobiofogy, we have solicited contributions that represent a broad spectrum of approaches and model systems in sensory biology. Some of these reviews describe mature and highly developed studies, whereas others offer a glimpse of what we hope to know in the near future. While it is impossible to cover all the exciting new work in sensory signaling in a single issue, we hope that this small selection highlights the beautiful biology and logic used by different sensory systems to orchestrate signaling, coding and processing.
Phototransduction The primary event in vision is the absorption of a photon of light by photoreceptor neurons in the retina. In vertebrates, light activation of the light receptor molecule, rhodopsin, activates a G protein that, in turn, activates a cGMP-phosphodiesterase (PDE). Active PDE hydrolyzes cGMP into GMP; the transient reduction in cGMP levels causes cation-selective channels on the photoreceptor membrane to close. Thus, the absorption of a photon of light by the vertebrate photoreceptor causes a brief hyperpolarization of the cell. Photoreceptor cells possess sophisticated biophysical properties, such as high sensitivity, high temporal resolution, and broad dynamic response range, that allow for efficient signal detection over a wide variety of light intensities. These properties are encoded in the elegant organization and regulation of the phototransduction cascade. High
sensitivity is endowed by the single-photon sensitivity of photoreceptors, while high temporal resolution is made possible by the efficient shut-off of each of the activated intermediates created during the excitation process, which ensures that the transduction machinery is quickly reset after generating a response. Although much is known about the activation phase of this cascade, several questions remain with respect to the basic mechanisms governing deactivation and adaptation. In this issue, Peter Detwiler and Mark Gray-Keller (pp 440-444) address some of these issues and suggest that adaptation results primarily from changes in the activation phase rather than in the recovery phase of the light response. Clearly, there will be several steps in the transduction cascade at which important regulatory events take place. With this in mind, Robert Molday (pp 445452) reviews work concerning the regulation of the light-activated channels (and the closely related olfactory cGMP-gated channels) by the Caz+-binding protein, calmodulin. As Caz+ is a key regulator of phototransduction, Molday highlights the interplay between Caz+ entry, Caz+ extrusion, the modulation of the cGMP-gated channels and the termination of the light response. The past few years have seen a renaissance in the field of mouse biology, largely driven by advances in mouse knock-out and knock-in technology. The study of phototransduction is no exception to this rule; Janis Lem and Clint Makino (pp 453-458) review recent uses of genetically engineered mice to dissect the functioning and regulation of this pathway in O~VO. Invertebrates, much like their vertebrate counterparts, have also evolved a highly sophisticated phototransducing machinery. The study on this process in Dmsophiia me/anogaster, a model ideally suited for molecular genetic and physiological manipulations in ~tio, offers the unique opportunity to dissect this pathway in an organism with tremendous versatility. Baruch Minke and Zvi Selinger (pp 459-466) review recent work dealing with one of the Drosophda light-activated channels and its potential role in Ca2+ homeostasis. This ion channel, TRP (transient receptor potential), has gained significant attention over the past year as it shares functional features common to the elusive family of store-operated channels implicated in refilling internal Ca2+ stores.
Processing In the standard textbook model of information flow in the vertebrate retina, photoreceptors make synapses with bipolar and horizontal cells, bipolar cells make synapses with amacrine cells and ganglion cells, and amacrine cells synapse onto ganglion cells. Implied in this model is
438
Sensory systems
a linear flow of information from a photoreceptor to a ganglion cell axon, with some lateral interactions. Richard Masland (pp 4671174) points out that such a simplification obscures some of the most interesting retinal processing. A quantitative census of cells reveals considerable convergence within the path to the output cells and shows, for instance, that the great majority of amacrine cells have not yet been identified. At the same time, new methods of multi-electrode recording have demonstrated sophisticated encoding of visual information, with much more information carried in the coincidence of firing in two or more axons. At the level of the primary visual cortex, the mechanism of conversion of simple center-surround receptive fields into oriented receptive fields in layer 4 has been controversial for decades. As Clay Reid and Jose-Manuel Alonso (pp 475-480) write, the original model of convergence of thalamic inputs appears to be correct. At the same time, the extensive horizontal connections within the cortex are becoming better understood.
Chemical senses The olfactory system provides a remarkable model for the study of information coding and information processing. The problem of how thousands of distinct olfactory receptors molecules distribute themselves among millions of olfactory sensory neurons, and how that information is encoded for faithful processing and integration in the olfactory bulb has been a central issue in neurobiology, Peter Mombaerts (pp 481486) reviews recent findings in this area and goes on to discuss some of the outstanding questions in the field. In addition to the main olfactory organ, most species have a separate, highly specialized accessory olfactory organ involved in pheromone signaling. Emily Liman (pp 487493) discusses the biology of pheromone transduction in the vomeronasal organ of vertebrates, and presents evidence that it is quite different from olfactory transduction. Despite the remarkable advances in our understanding of the biology of olfaction in vertebrates, we still know little about the molecular mechanisms of olfaction in invertebrates. Interestingly, recent progress in the nematode Gaenorhabditi et’egans is providing wonderful insight into the function of olfactory receptor genes and the organization of olfactory circuits. In this issue, Joshua Kaplan (pp 494-499) reviews sensory signaling in G. elegans, and Dean Smith (pp 500-505) reviews the genetics and physiology of olfaction in the fruit fly Drosophila melanogaster. Taste transduction is one of the most sophisticated forms of chemotransduction in higher organisms. Gustatory signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates; its
main purpose is to provide a reliable signaling response to non-volatile chemicals. Higher organisms have four basic types of taste modalities: salty, sour, sweet and bitter-umami, the taste elicited by glutamate, is often considered a fifth modality. Each of these is thought to be mediated by distinct signaling pathways leading to receptor cell activation. Sue Kinnamon and Robert Margolskee (pp 506-513) review the field of gustatory with particular emphasis on models of transduction, signaling mechanisms in the different taste modalities.
Mechanoreception
and pain
The conversion of sound into neural signals by hair cells of the inner ear has become much better understood in the past decade. While much of the attention has been focused on the transduction by mechanosensitive ion channels in the hair bundle, equally remarkable are the afferent and efferent synapses at the basal pole of the hair cell, reviewed here by Paul Fuchs (pp 514-519). At the afferent synapse, release of transmitter by the hair cell is tonic-unlike impulsive transmission, it occurs continuously and its rate is modulated by membrane potential. The proteins specialized for this synapse are begin,ning to be identified. The efferent synapse (feedback from the brainstem to hair cells) is cholinergic but is usually inhibitory. Elegant work in recent years has revealed the mechanism (Caz+ influx through a novel nicotinic receptor activating a larger outward K+ flux) and has raised the issue of whether cholinergic transmission in the CNS may often be inhibitory. Other proteins involved in hair cell function and in the morphogenesis of inner ear organs have been identified by studying inherited deafness. Karen Steel and Stephen Brown (pp 520-525) describe the explosive growth in identified deafness genes, both in humans and mutant mice. They demonstrate also the power in correlating homologous genes between mouse and human. In contrast to the elucidation of mechanotransduction in the inner ear, our grasp of transduction by primary sensory neurons of the dorsal root ganglia has been slow: the sensory endings are small, are embedded among cells of the skin, and do not have particularly obvious morphological features that offer clues to function. Nociception by dorsal root ganglion neurons (which translates into pain perception) might be expected to be the most difficult to understand because ‘noxious’ stimuli are not clearly defined. Geoffrey Burnstock and John Wood (pp 526-532) summarize evidence for an elegantly simple hypothesis for nociception - that noxious stimuli are those that damage other cells enough to cause ATP release, and that these neurons express a specific ATP receptor channel that generates a receptor potential.
Cell fate The extraordinary morphological complexity of the eye and the inner ear prompts the question of how such organs
Editorial overview Corey and Zuker
could develop. For a long time, the factors driving the development of the inner ear were not well understood; very recently, however, there has been rapid progress in this field. Donna Fekete (pp 533-541) describes several stages of inner ear development: the three-dimensional morphogenesis that converts a flat sheet of cells to a labyrinthine set of tubes and sacks, the specification of sensory regions within the labyrinth, the specification of hair cells within those regions, and the development and maintenance of synaptic connections with hair cells. She proposes a new model for how the sensory epithelia become specified. For each of these stages, the molecules responsible for specifying fate are rapidly becoming known.
439
In the retina, the development is better understood, but the more specific cell fate decisions are still unclear. Constance Cepko (pp 542-546) considers the question of how a photoreceptor decides what kind of photoreceptor to become (for instance, a red, green or blue cone), and compares expression of particular opsin genes with factors such as a cell’s position in the retina or birth date. Some of these reviews summarize the answers to longstanding questions, whereas others serve to illuminate the beginnings of rapid progress in a field. All convey the extraordinary excitement of working in sensory neuroscience in this decade, and the promise of revelations to come.
Sensory systems Editorial overview David P Corey’ and Charles S Zuker* Addresses ‘Howard Hughes Medical Institute and Department of Neurobiology, Wellman 414, Massachusetts General Hospital, Boston, Massachusetts 02114, USA, e-mail: [email protected] 2Howard Hughes Medical Institute and Departments of Biology and Neuroscience, University of California at San Diego, La Jolla, California 92093, USA; e-mail: [email protected] Abbreviation PDE cGMP-phosphodiesterase
Current Opinion in Neurobiology 1996, 6:437-439 0 Current Biology Ltd ISSN 0959-4388
Introduction The study of sensory systems dates back several centuries, beginning with primitive, descriptive studies of pain sensation, extending to current sophisticated experiments that analyze the coding of sensory information in the CNS. The past few years have witnessed a tremendous progress in the field, fueled by advances in technology combined with new insights into the cellular and molecular biology of sensory receptor cells. For this issue of Current Opinion in Neurobiofogy, we have solicited contributions that represent a broad spectrum of approaches and model systems in sensory biology. Some of these reviews describe mature and highly developed studies, whereas others offer a glimpse of what we hope to know in the near future. While it is impossible to cover all the exciting new work in sensory signaling in a single issue, we hope that this small selection highlights the beautiful biology and logic used by different sensory systems to orchestrate signaling, coding and processing.
Phototransduction The primary event in vision is the absorption of a photon of light by photoreceptor neurons in the retina. In vertebrates, light activation of the light receptor molecule, rhodopsin, activates a G protein that, in turn, activates a cGMP-phosphodiesterase (PDE). Active PDE hydrolyzes cGMP into GMP; the transient reduction in cGMP levels causes cation-selective channels on the photoreceptor membrane to close. Thus, the absorption of a photon of light by the vertebrate photoreceptor causes a brief hyperpolarization of the cell. Photoreceptor cells possess sophisticated biophysical properties, such as high sensitivity, high temporal resolution, and broad dynamic response range, that allow for efficient signal detection over a wide variety of light intensities. These properties are encoded in the elegant organization and regulation of the phototransduction cascade. High
sensitivity is endowed by the single-photon sensitivity of photoreceptors, while high temporal resolution is made possible by the efficient shut-off of each of the activated intermediates created during the excitation process, which ensures that the transduction machinery is quickly reset after generating a response. Although much is known about the activation phase of this cascade, several questions remain with respect to the basic mechanisms governing deactivation and adaptation. In this issue, Peter Detwiler and Mark Gray-Keller (pp 440-444) address some of these issues and suggest that adaptation results primarily from changes in the activation phase rather than in the recovery phase of the light response. Clearly, there will be several steps in the transduction cascade at which important regulatory events take place. With this in mind, Robert Molday (pp 445452) reviews work concerning the regulation of the light-activated channels (and the closely related olfactory cGMP-gated channels) by the Caz+-binding protein, calmodulin. As Caz+ is a key regulator of phototransduction, Molday highlights the interplay between Caz+ entry, Caz+ extrusion, the modulation of the cGMP-gated channels and the termination of the light response. The past few years have seen a renaissance in the field of mouse biology, largely driven by advances in mouse knock-out and knock-in technology. The study of phototransduction is no exception to this rule; Janis Lem and Clint Makino (pp 453-458) review recent uses of genetically engineered mice to dissect the functioning and regulation of this pathway in O~VO. Invertebrates, much like their vertebrate counterparts, have also evolved a highly sophisticated phototransducing machinery. The study on this process in Dmsophiia me/anogaster, a model ideally suited for molecular genetic and physiological manipulations in ~tio, offers the unique opportunity to dissect this pathway in an organism with tremendous versatility. Baruch Minke and Zvi Selinger (pp 459-466) review recent work dealing with one of the Drosophda light-activated channels and its potential role in Ca2+ homeostasis. This ion channel, TRP (transient receptor potential), has gained significant attention over the past year as it shares functional features common to the elusive family of store-operated channels implicated in refilling internal Ca2+ stores.
Processing In the standard textbook model of information flow in the vertebrate retina, photoreceptors make synapses with bipolar and horizontal cells, bipolar cells make synapses with amacrine cells and ganglion cells, and amacrine cells synapse onto ganglion cells. Implied in this model is
438
Sensory systems
a linear flow of information from a photoreceptor to a ganglion cell axon, with some lateral interactions. Richard Masland (pp 4671174) points out that such a simplification obscures some of the most interesting retinal processing. A quantitative census of cells reveals considerable convergence within the path to the output cells and shows, for instance, that the great majority of amacrine cells have not yet been identified. At the same time, new methods of multi-electrode recording have demonstrated sophisticated encoding of visual information, with much more information carried in the coincidence of firing in two or more axons. At the level of the primary visual cortex, the mechanism of conversion of simple center-surround receptive fields into oriented receptive fields in layer 4 has been controversial for decades. As Clay Reid and Jose-Manuel Alonso (pp 475-480) write, the original model of convergence of thalamic inputs appears to be correct. At the same time, the extensive horizontal connections within the cortex are becoming better understood.
Chemical senses The olfactory system provides a remarkable model for the study of information coding and information processing. The problem of how thousands of distinct olfactory receptors molecules distribute themselves among millions of olfactory sensory neurons, and how that information is encoded for faithful processing and integration in the olfactory bulb has been a central issue in neurobiology, Peter Mombaerts (pp 481486) reviews recent findings in this area and goes on to discuss some of the outstanding questions in the field. In addition to the main olfactory organ, most species have a separate, highly specialized accessory olfactory organ involved in pheromone signaling. Emily Liman (pp 487493) discusses the biology of pheromone transduction in the vomeronasal organ of vertebrates, and presents evidence that it is quite different from olfactory transduction. Despite the remarkable advances in our understanding of the biology of olfaction in vertebrates, we still know little about the molecular mechanisms of olfaction in invertebrates. Interestingly, recent progress in the nematode Gaenorhabditi et’egans is providing wonderful insight into the function of olfactory receptor genes and the organization of olfactory circuits. In this issue, Joshua Kaplan (pp 494-499) reviews sensory signaling in G. elegans, and Dean Smith (pp 500-505) reviews the genetics and physiology of olfaction in the fruit fly Drosophila melanogaster. Taste transduction is one of the most sophisticated forms of chemotransduction in higher organisms. Gustatory signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates; its
main purpose is to provide a reliable signaling response to non-volatile chemicals. Higher organisms have four basic types of taste modalities: salty, sour, sweet and bitter-umami, the taste elicited by glutamate, is often considered a fifth modality. Each of these is thought to be mediated by distinct signaling pathways leading to receptor cell activation. Sue Kinnamon and Robert Margolskee (pp 506-513) review the field of gustatory with particular emphasis on models of transduction, signaling mechanisms in the different taste modalities.
Mechanoreception
and pain
The conversion of sound into neural signals by hair cells of the inner ear has become much better understood in the past decade. While much of the attention has been focused on the transduction by mechanosensitive ion channels in the hair bundle, equally remarkable are the afferent and efferent synapses at the basal pole of the hair cell, reviewed here by Paul Fuchs (pp 514-519). At the afferent synapse, release of transmitter by the hair cell is tonic-unlike impulsive transmission, it occurs continuously and its rate is modulated by membrane potential. The proteins specialized for this synapse are begin,ning to be identified. The efferent synapse (feedback from the brainstem to hair cells) is cholinergic but is usually inhibitory. Elegant work in recent years has revealed the mechanism (Caz+ influx through a novel nicotinic receptor activating a larger outward K+ flux) and has raised the issue of whether cholinergic transmission in the CNS may often be inhibitory. Other proteins involved in hair cell function and in the morphogenesis of inner ear organs have been identified by studying inherited deafness. Karen Steel and Stephen Brown (pp 520-525) describe the explosive growth in identified deafness genes, both in humans and mutant mice. They demonstrate also the power in correlating homologous genes between mouse and human. In contrast to the elucidation of mechanotransduction in the inner ear, our grasp of transduction by primary sensory neurons of the dorsal root ganglia has been slow: the sensory endings are small, are embedded among cells of the skin, and do not have particularly obvious morphological features that offer clues to function. Nociception by dorsal root ganglion neurons (which translates into pain perception) might be expected to be the most difficult to understand because ‘noxious’ stimuli are not clearly defined. Geoffrey Burnstock and John Wood (pp 526-532) summarize evidence for an elegantly simple hypothesis for nociception - that noxious stimuli are those that damage other cells enough to cause ATP release, and that these neurons express a specific ATP receptor channel that generates a receptor potential.
Cell fate The extraordinary morphological complexity of the eye and the inner ear prompts the question of how such organs
Editorial overview Corey and Zuker
could develop. For a long time, the factors driving the development of the inner ear were not well understood; very recently, however, there has been rapid progress in this field. Donna Fekete (pp 533-541) describes several stages of inner ear development: the three-dimensional morphogenesis that converts a flat sheet of cells to a labyrinthine set of tubes and sacks, the specification of sensory regions within the labyrinth, the specification of hair cells within those regions, and the development and maintenance of synaptic connections with hair cells. She proposes a new model for how the sensory epithelia become specified. For each of these stages, the molecules responsible for specifying fate are rapidly becoming known.
439
In the retina, the development is better understood, but the more specific cell fate decisions are still unclear. Constance Cepko (pp 542-546) considers the question of how a photoreceptor decides what kind of photoreceptor to become (for instance, a red, green or blue cone), and compares expression of particular opsin genes with factors such as a cell’s position in the retina or birth date. Some of these reviews summarize the answers to longstanding questions, whereas others serve to illuminate the beginnings of rapid progress in a field. All convey the extraordinary excitement of working in sensory neuroscience in this decade, and the promise of revelations to come.