- Email: [email protected]
Special Issue on “Functional Anatomy of Ear Connections”
Brain Research Bulletin 60 (2003) 395–396
Foreword
Special Issue on “Functional Anatomy of Ear Connections” This volume is dedicated to the memory of Rafael Lorente de Nó, a great pioneer of the functional neuroanatomy of the inner ear (1902–1990). Starting in 1926 [2], R. Lorente de Nó published a remarkable series of papers, outlining in great detail all his findings on the peripheral and central termination of the vestibular and cochlear nerve, as well as the embryology of these neurons and their fiber growth. This work was summarized in English [3] and remains to date the last time that all of these functional anatomical aspects of the mammalian ear and their development were brought together in a single article. In the 70 years between this last summary of the functional anatomy of the mammalian ear and its development, much progress has been made. Consequently, it would be impossible for a single author to authoritatively cover this ever increasing field of emerging subdisciplines of inner ear research. The present special issue was conceived in an attempt to bring together reviews on various aspects of peripheral and central organization of the auditory and vestibular system and its development during the centennial anniversary of Lorente. As it were, a parallel endeavor provided an up-to-date authoritative functional anatomical review of the vestibular periphery [5] and this aspect has therefore been dropped from the current issue. Nevertheless, it is important to stress that despite several years of denial of some of Lorente’s findings (three distinct nerve fibers should innervate only two distinct types of hair cells recognizable by transmission electron microscopy), it was only recently confirmed using single fiber filling. Now we know that each vestibular sensory epithelium in mammals consists of two types of hair cells with distinct patterns of distribution, polarity, and physiology [5]. These hair cells are innervated by three different afferent fibers—thick fibers forming large calyceal endings around type I hair cells, thin fibers which end exclusively as boutons on type II hair cells, and medium sized fibers that innervate type I hair cells with a calyx but also innervate type II hair cells with branches—that form terminal boutons. The third type of afferent is referred to as dimorphic. While Lorente could recognize these three nerve fibers in his Golgi preparations, it was impossible for him to reconstruct the spatial pattern of fiber distribution in the vestibular endorgans in detail, in his sections. Nevertheless, Lorente recognized regional aspects in the maculae of the
utricle and saccule and the cristae of the canals. In mammals, such regional differences are now known as striola versus extrastriolar differences and reflect the distribution of large calyceal endings (striola only), dimorphic endings (randomly throughout the sensory epithelium), and bouton endings (only in extrastriolar regions). In the cristae, which lack the striola with the reversal in hair cell polarity, calyx endings are in the center, dimorphic endings scattered throughout, and bouton only endings are at the periphery, somewhat similar to Lorente’s proposal some 70 years ago. The reader interested in the physiological differences of these fibers and their functional significance is referred to the paper of Lysakowski and Goldberg [5]. Lorente was particularly interested in the development of the peripheral innervation. This special issue includes a review (by Fritzsch) that outlines the molecular and developmental aspects of vestibular endorgan innervation, building on the detailed descriptive analysis of Lorente de Nó [2]. Recent years have seen dramatic progress in understanding the molecular basis of sensory neuron formation and maintenance by neurotrophins. However, comparatively little is known about the development of various fiber types and how their specific pattern of innervation is guided during development. A recent review has summarized the development of the cochlea spiral neurons and the reader is referred to that paper for details [8]. Several recent reviews exist on the efferent system to the vestibular epithelia [1,5], a system not recognized by Lorente or any of his contemporaries. This system has therefore been omitted entirely in the present issue. Recent tract tracing data suggest an even more complex distribution of regional specific fibers to various areas of the brain, in particular the cerebellum [6,7]. Such data require further analysis before the functional significance is fully understood. It is, however, safe to say that, while over 100 years of research into afferent termination and its functional significance have revealed a large body of information, it may still harbor some surprises in the way this peripheral diversity is mapped onto the central nervous system. Mining this information requires more sophisticated bidirectional tracer studies using modern techniques. This special issue contains two review articles that deal with the functional anatomy of the vestibular projection into the vestibular nuclei and the vestibular cerebellum (the review paper by Newlands and Perachio) with the functional
0361-9230/03/$ – see front matter © 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0361-9230(03)00046-7
396
Foreword / Brain Research Bulletin 60 (2003) 395–396
neuroanatomy of vestibular nuclei connections and interconnections with the cerebellum (the review paper by Barmack). Both review articles present the state of the art in these two areas and go well beyond the insights generated by Lorente’s work. Still, the basic wiring of the three neuron reflex arc (primary and secondary vestibular neuron, oculomotor motoneurons) remains as described by Lorente and his contemporary Poljak in the 1920s. However, both reviews stress the current level of complexity of these connections, using modern tracing and physiological techniques, and also emphasize our ignorance concerning many aspects of the detailed neuroanatomy of first and second order connections. A third review (by Maklad and Fritzsch) outlines the molecular mechanisms that guide the development of these connections. Given the multifaceted function of the primary terminals and second order output neurons, the not yet fully explored levels of interaction between linear and angular acceleration perceived mainly by the macular and cristae organs, respectively, it is not surprising to find that both segregated projections, as well as overlapping areas, form apparently governed by not yet understood genetic guidance cues. Clearly, more work is needed to align development with adult functional neuroanatomy of vestibular nuclei connectivity. A second component of the ear is the auditory system, represented in the ear by the cochlea and the innervating neurons of the spiral ganglion, and the central auditory nuclei and their output. Lorente de Nó noticed the regular projection of spiral fibers to distinct regions of the cochlea as well as discrete longitudinal stripes of the cochlear nuclei, as early as 1926 [2]. However, only through the interaction with Polyak did Lorente reach the conclusion that topological precise connections between the cochlea and the cochlear nuclei are the basis for frequency-specific hearing [3,4]. Combined with later work by many others, this led to the current level of understanding of the tonotopic organization of the entire auditory system. Three reviews in this issue deal with the organization of the organ of Corti and its ever increasing cellular and molecular complexity, that provides the basis for this frequency-specific perception along the length of the cochlea (see the review article by Raphael and Altschuler). As with the vestibular system, two types of hair cells (inner and outer hair cells) and two types of afferents (type I to inner hair cells; type II to outer hair cells) are recognized in the cochlea. A second review explores the central projection, showing the intricate details of afferent termination in both mammals and chicken. Those terminals show remarkable similarities which likely reflect functional convergence between these two lines of vertebrates (see the review article by Ryugo and Parks). Most interesting is the detailed functional neuroanatomy of the type I spiral afferents on the rich cellular diversity of neurons of the three cochlear nuclei. A third review (by Kant) deals with the cellular organization of these three auditory nuclei and their output, detailing the increased complexity of multiple levels of auditory output not only to brainstem
nuclei en route to the auditory cortex but also to many other nuclei. Comparison of these review articles (by Kant, and by Ryugo and Parks, respectively) with the cellular analysis of Lorente de Nó [4] shows the remarkable progress that has been achieved in the functional anatomical understanding of the system that was a starting point for the investigations of Lorente. However, comparing these most recent insights with the original work of Lorente in this area can only make us appreciate the profound insights this young medical student had single handedly achieved some 70 years ago using the Golgi technique. As the Guest Editor, I wish to thank all the contributors for their energy and time to make this special edition a reality. Dr. Marina Bentivoglio helped in many editorial aspects that shaped this volume, and her timeless commitment to answer emails about details of the publishing procedure and other matters is very much appreciated by all contributors. We are all indebted to the several reviewers who spend time pouring over initial drafts and suggested improvements to turn them into better papers. Without their commitment to science this issue would not have materialized in the way it did.
References [1] B. Fritzsch, Ontogenetic and evolutionary evidence for the motoneuron nature of vestibular and cochlear efferents, in: C.I. Berlin (Ed.), The Efferent Auditory System: Basic Science and Clinical Applications, Singular Publishing, San Diego, 1999, pp. 31–59. [2] R. Lorente de Nó, Etudes sur l’anatomie et la physiologie du labyrinthe de l’oreille et du VIII nerf. II. Quelques données au sujet de l’anatomie des organes sensoriels du labyrinthe, Trav. Lab. Rech. Biol. Univ. Madrid 24 (1926) 53–153. [3] R. Lorente de Nó, Anatomy of the eighth nerve: the central projections of the nerve endings of the internal ear, Laryngoscope 43 (1933) 1–38. [4] R. Lorente de Nó, The Primary Acoustic Nuclei, Raven Press, New York, 1981, p. 177. [5] A.L. Lysakowski, J.M. Goldberg, Morphophysiology of the Vestibular Periphery, in: S. Highstein, A.N. Popper, R.R. Fay (Eds.), The Anatomy and Physiology of the Central and Peripheral Vestibular System, Springer, New York, 2003. [6] A. Maklad, B. Fritzsch, Partial segregation of posterior crista and saccular fibers to the nodulus and uvula of the cerebellum in mice, and its development, Dev. Brain Res. 140 (2003) 223–236. [7] I.M. Purcell, A.A. Perachio, Peripheral patterns of terminal innervation of vestibular primary afferent neurons projecting to the vestibulocerebellum in the gerbil, J. Comp. Neurol. 433(2001) 48–61. [8] E.W. Rubel, B. Fritzsch, Auditory system development: primary auditory neurons and their targets, Annu. Rev. Neurosci. 25 (2002) 51–101.
Bernd Fritzsch Department of Biomedical Sciences Creighton University, Omaha, NE 68178, USA Tel.: +1-402-280-2915; fax: +1-402-280-5556 E-mail address: [email protected]
Foreword
Special Issue on “Functional Anatomy of Ear Connections” This volume is dedicated to the memory of Rafael Lorente de Nó, a great pioneer of the functional neuroanatomy of the inner ear (1902–1990). Starting in 1926 [2], R. Lorente de Nó published a remarkable series of papers, outlining in great detail all his findings on the peripheral and central termination of the vestibular and cochlear nerve, as well as the embryology of these neurons and their fiber growth. This work was summarized in English [3] and remains to date the last time that all of these functional anatomical aspects of the mammalian ear and their development were brought together in a single article. In the 70 years between this last summary of the functional anatomy of the mammalian ear and its development, much progress has been made. Consequently, it would be impossible for a single author to authoritatively cover this ever increasing field of emerging subdisciplines of inner ear research. The present special issue was conceived in an attempt to bring together reviews on various aspects of peripheral and central organization of the auditory and vestibular system and its development during the centennial anniversary of Lorente. As it were, a parallel endeavor provided an up-to-date authoritative functional anatomical review of the vestibular periphery [5] and this aspect has therefore been dropped from the current issue. Nevertheless, it is important to stress that despite several years of denial of some of Lorente’s findings (three distinct nerve fibers should innervate only two distinct types of hair cells recognizable by transmission electron microscopy), it was only recently confirmed using single fiber filling. Now we know that each vestibular sensory epithelium in mammals consists of two types of hair cells with distinct patterns of distribution, polarity, and physiology [5]. These hair cells are innervated by three different afferent fibers—thick fibers forming large calyceal endings around type I hair cells, thin fibers which end exclusively as boutons on type II hair cells, and medium sized fibers that innervate type I hair cells with a calyx but also innervate type II hair cells with branches—that form terminal boutons. The third type of afferent is referred to as dimorphic. While Lorente could recognize these three nerve fibers in his Golgi preparations, it was impossible for him to reconstruct the spatial pattern of fiber distribution in the vestibular endorgans in detail, in his sections. Nevertheless, Lorente recognized regional aspects in the maculae of the
utricle and saccule and the cristae of the canals. In mammals, such regional differences are now known as striola versus extrastriolar differences and reflect the distribution of large calyceal endings (striola only), dimorphic endings (randomly throughout the sensory epithelium), and bouton endings (only in extrastriolar regions). In the cristae, which lack the striola with the reversal in hair cell polarity, calyx endings are in the center, dimorphic endings scattered throughout, and bouton only endings are at the periphery, somewhat similar to Lorente’s proposal some 70 years ago. The reader interested in the physiological differences of these fibers and their functional significance is referred to the paper of Lysakowski and Goldberg [5]. Lorente was particularly interested in the development of the peripheral innervation. This special issue includes a review (by Fritzsch) that outlines the molecular and developmental aspects of vestibular endorgan innervation, building on the detailed descriptive analysis of Lorente de Nó [2]. Recent years have seen dramatic progress in understanding the molecular basis of sensory neuron formation and maintenance by neurotrophins. However, comparatively little is known about the development of various fiber types and how their specific pattern of innervation is guided during development. A recent review has summarized the development of the cochlea spiral neurons and the reader is referred to that paper for details [8]. Several recent reviews exist on the efferent system to the vestibular epithelia [1,5], a system not recognized by Lorente or any of his contemporaries. This system has therefore been omitted entirely in the present issue. Recent tract tracing data suggest an even more complex distribution of regional specific fibers to various areas of the brain, in particular the cerebellum [6,7]. Such data require further analysis before the functional significance is fully understood. It is, however, safe to say that, while over 100 years of research into afferent termination and its functional significance have revealed a large body of information, it may still harbor some surprises in the way this peripheral diversity is mapped onto the central nervous system. Mining this information requires more sophisticated bidirectional tracer studies using modern techniques. This special issue contains two review articles that deal with the functional anatomy of the vestibular projection into the vestibular nuclei and the vestibular cerebellum (the review paper by Newlands and Perachio) with the functional
0361-9230/03/$ – see front matter © 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0361-9230(03)00046-7
396
Foreword / Brain Research Bulletin 60 (2003) 395–396
neuroanatomy of vestibular nuclei connections and interconnections with the cerebellum (the review paper by Barmack). Both review articles present the state of the art in these two areas and go well beyond the insights generated by Lorente’s work. Still, the basic wiring of the three neuron reflex arc (primary and secondary vestibular neuron, oculomotor motoneurons) remains as described by Lorente and his contemporary Poljak in the 1920s. However, both reviews stress the current level of complexity of these connections, using modern tracing and physiological techniques, and also emphasize our ignorance concerning many aspects of the detailed neuroanatomy of first and second order connections. A third review (by Maklad and Fritzsch) outlines the molecular mechanisms that guide the development of these connections. Given the multifaceted function of the primary terminals and second order output neurons, the not yet fully explored levels of interaction between linear and angular acceleration perceived mainly by the macular and cristae organs, respectively, it is not surprising to find that both segregated projections, as well as overlapping areas, form apparently governed by not yet understood genetic guidance cues. Clearly, more work is needed to align development with adult functional neuroanatomy of vestibular nuclei connectivity. A second component of the ear is the auditory system, represented in the ear by the cochlea and the innervating neurons of the spiral ganglion, and the central auditory nuclei and their output. Lorente de Nó noticed the regular projection of spiral fibers to distinct regions of the cochlea as well as discrete longitudinal stripes of the cochlear nuclei, as early as 1926 [2]. However, only through the interaction with Polyak did Lorente reach the conclusion that topological precise connections between the cochlea and the cochlear nuclei are the basis for frequency-specific hearing [3,4]. Combined with later work by many others, this led to the current level of understanding of the tonotopic organization of the entire auditory system. Three reviews in this issue deal with the organization of the organ of Corti and its ever increasing cellular and molecular complexity, that provides the basis for this frequency-specific perception along the length of the cochlea (see the review article by Raphael and Altschuler). As with the vestibular system, two types of hair cells (inner and outer hair cells) and two types of afferents (type I to inner hair cells; type II to outer hair cells) are recognized in the cochlea. A second review explores the central projection, showing the intricate details of afferent termination in both mammals and chicken. Those terminals show remarkable similarities which likely reflect functional convergence between these two lines of vertebrates (see the review article by Ryugo and Parks). Most interesting is the detailed functional neuroanatomy of the type I spiral afferents on the rich cellular diversity of neurons of the three cochlear nuclei. A third review (by Kant) deals with the cellular organization of these three auditory nuclei and their output, detailing the increased complexity of multiple levels of auditory output not only to brainstem
nuclei en route to the auditory cortex but also to many other nuclei. Comparison of these review articles (by Kant, and by Ryugo and Parks, respectively) with the cellular analysis of Lorente de Nó [4] shows the remarkable progress that has been achieved in the functional anatomical understanding of the system that was a starting point for the investigations of Lorente. However, comparing these most recent insights with the original work of Lorente in this area can only make us appreciate the profound insights this young medical student had single handedly achieved some 70 years ago using the Golgi technique. As the Guest Editor, I wish to thank all the contributors for their energy and time to make this special edition a reality. Dr. Marina Bentivoglio helped in many editorial aspects that shaped this volume, and her timeless commitment to answer emails about details of the publishing procedure and other matters is very much appreciated by all contributors. We are all indebted to the several reviewers who spend time pouring over initial drafts and suggested improvements to turn them into better papers. Without their commitment to science this issue would not have materialized in the way it did.
References [1] B. Fritzsch, Ontogenetic and evolutionary evidence for the motoneuron nature of vestibular and cochlear efferents, in: C.I. Berlin (Ed.), The Efferent Auditory System: Basic Science and Clinical Applications, Singular Publishing, San Diego, 1999, pp. 31–59. [2] R. Lorente de Nó, Etudes sur l’anatomie et la physiologie du labyrinthe de l’oreille et du VIII nerf. II. Quelques données au sujet de l’anatomie des organes sensoriels du labyrinthe, Trav. Lab. Rech. Biol. Univ. Madrid 24 (1926) 53–153. [3] R. Lorente de Nó, Anatomy of the eighth nerve: the central projections of the nerve endings of the internal ear, Laryngoscope 43 (1933) 1–38. [4] R. Lorente de Nó, The Primary Acoustic Nuclei, Raven Press, New York, 1981, p. 177. [5] A.L. Lysakowski, J.M. Goldberg, Morphophysiology of the Vestibular Periphery, in: S. Highstein, A.N. Popper, R.R. Fay (Eds.), The Anatomy and Physiology of the Central and Peripheral Vestibular System, Springer, New York, 2003. [6] A. Maklad, B. Fritzsch, Partial segregation of posterior crista and saccular fibers to the nodulus and uvula of the cerebellum in mice, and its development, Dev. Brain Res. 140 (2003) 223–236. [7] I.M. Purcell, A.A. Perachio, Peripheral patterns of terminal innervation of vestibular primary afferent neurons projecting to the vestibulocerebellum in the gerbil, J. Comp. Neurol. 433(2001) 48–61. [8] E.W. Rubel, B. Fritzsch, Auditory system development: primary auditory neurons and their targets, Annu. Rev. Neurosci. 25 (2002) 51–101.
Bernd Fritzsch Department of Biomedical Sciences Creighton University, Omaha, NE 68178, USA Tel.: +1-402-280-2915; fax: +1-402-280-5556 E-mail address: [email protected]