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dc.contributor.authorMukerji, Sudeep
dc.date.accessioned2016-05-11T11:58:18Z
dc.date.available2016-05-11T11:58:18Z
dc.date.issued2016-04-29
dc.identifier.isbn978-82-308-3341-4
dc.identifier.urihttp://hdl.handle.net/1956/11988
dc.description.abstract<p>Backgroun. In the auditory brainstem of mammals, there are two main descending reflex systems to the auditory system; The middle ear muscle reflex and the olivocochlear reflex. The two middle ear muscles participating in the middle ear muscle reflex are the stapedius and the tensor tympani. In man, the stapedius is known to react to strong low frequency acoustic stimulation, enacting forces perpendicular to the stapes superstructure, increasing middle ear impedance and reducing the intensity of acoustic energy arriving at the cochlea of the inner ear. Unlike the stapedius, the tensor tympani muscle has been proven to contract in response to self-generated noise such as chewing, swallowing and other non-auditory stimuli. The first theories on tensor tympani function were created by the a 16th Century Italian anatomist and scientist called Hieronymous Fabricius (1533-1619). He was the first to allude to both an auditory and non-auditory role of the tensor tympani muscle in humans. Since his work, many theories have been created founded on an evolving ability to analyze the components of the middle ear reflex pathways of the brainstem using various labeling techniques. It is now known that transduction of sound happens in the cochlea, causing an action potential that is sent along the auditory nerve to the cochlear nucleus in the brainstem. The cochlear nucleus is the first relay station for all ascending sound information originating in the ear. Unknown interneurons in the ventral cochlear nucleus then spread either directly or indirectly to the multiple middle ear muscle motoneurons located elsewhere in the brainstem. These motoneurons provide efferent innervation to the stapedius and the tensor tympani. There are many interesting differences among species in the acoustic thresholds for contraction of the middle ear muscles, which may be a reflection of underlying anatomical and physiological differences such as the number of tensor tympani muscle motoneurons. The goal of one of our research studies was to investigate the quantity, location and morphological characteristics of the tensor tympani motoneurons in the mouse model. Although the ascending and descending limbs of these reflex pathways have been described, the identity of the reflex interneurons within the reflex pathway is still unknown, as are the sources of modulatory inputs to these pathways. Olivocochlear neurons participate in the olivocochlear reflex pathway. They react to acoustic stimulation and provide descending input that controls auditory processing in the cochlea. As in the middle ear muscle reflex, the identities of these neurons in the pathways providing inputs to olivocochlear neurons are also incompletely understood and similar labeling techniques were used to further study these interneurons. Furthermore, we relate our findings to the unpublished results off recent experiments that used infrared light as a means of stimulating the auditory brainstem as a possible technology in future clinical applications of brainstem implants. </p> <p>Materials and methods. This work consists primarily of four papers of which two are based on research that focuses on the anatomical geography (and postulated function) of the middle ear and the olivocochlear reflex pathways. The animal models in each investigation were mice and guinea pig. For the tensor tympani muscle reflex experiments, we used the chemical trans-synaptic tracer called Fluorogold to retrogradely label cell bodies and their dendrites in mice. For the olivocochlear reflex experiments, we also used a retrograde transneuronal tracer but in the form of a pseudorabies virus (Bartha strain, expressing green fluorescent protein) to label neurons and their input in guinea pigs. These animal models have become the most common subjects for auditory and neuroscience research based on many factors, both biological and practical. The mouse and guinea pig were chosen because of the large availability of genetically altered strains in neuroscience research. Their relatively short lifespan renders them preferable for studies on the effects of aging. Furthermore, the very high frequency range of the hearing in mice vs. the low-frequency effects of middle ear muscle contraction makes it interesting to speculate on the functional roles of middle ear muscles in this species. The aim of the scientific papers was to provide an overview of the middle ear muscle reflex anatomy and physiology, to present new data on the middle ear muscle reflex anatomy and physiology, to describe the clinical implications of our research and to dedicate some attention to the historical efforts of research on the middle ear muscles, especially the tensor tympani. The latter was achieved by studying the original theories presented on tensor tympani function postulated by a renowned Italian anatomist/scientist named Hieronymous Fabricius (1533-1619). These theories, translated from Latin, were analyzed from his book “De Visione, Voce et Auditu” (The vision, voice and hearing) first published in 1600 and access to which was gained with scheduled permission from the Harvard Center for Rare Books, Cambridge (Massachusetts, USA). </p> <p>Results and conclusions. After injections of Fluorogold into the tensor tympani muscle, a column of labeled tensor tympani motoneurons (TTMNs) was identified ventro-lateral to the ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to their morphological characteristics into three subtypes: “octopus-like”, “fusiform” and “stellate”, suggesting underlying differences in function. All three subtypes formed sparsely branched and radiating dendrites, some longer than 600 μm. Dendrites were longest and most numerous in the dorso-medial direction, stretching into non-auditory regions of the brainstem. The long dendrites and the various subtypes of TTMNs support the idea that contraction of the tensor tympani muscle can be secondary to multiple non-auditory inputs. Our findings agree with past experiments showing that the labeled TTMNs were found just outside the trigeminal motor nucleus, probably forming part of a separate “tensor tympani motor nucleus of V”. This separate nucleus was distinct from the trigeminal motor nucleus in term of cellular composition and orientation. To explore the olivocochlear pathways, the retrograde transneuronal tracer pseudorabies virus (Bartha strain, expressing green fluorescent protein) was used successfully to label neurons and their inputs in guinea pigs. Labeling of olivocochlear neurons started on the first day after injection into the cochlea. On the second day (and for longer survival times), transneuronal labeling spread to the cochlear nucleus, inferior colliculus, and other brainstem areas. There was a relationship between the numbers of these transneuronally labeled neurons and the number of labeled medial olivocochlear neurons, implying that the spread of labeling proceeds predominantly via synapses on the medial olivocochlear neurons. In the cochlear nucleus, the transneuronally labeled neurons were classified as “multipolar” cells including the subtype known as “planar” cells. In the central nucleus of the inferior colliculus, transneuronally labeled neurons were of two principal types: neurons with disc-shaped dendritic fields and neurons with dendrites in a stellate pattern. Transneuronal labeling was also observed in pyramidal cells in the auditory cortex and in centers not typically associated with the auditory pathway such as the pontine reticular formation, subcoerulean nucleus, and the pontine dorsal raphe. These data presents us more information on the identity of neurons providing input to auditory neurons, which are located in auditory as well as non-auditory centers. Additionally, we learnt from translated written accounts that Fabricius was a pioneer in approaching anatomy from a structure-function relationship and that he was an active proponent for improving the learning environment for students. The writings of Fabricius on the middle ear also provided the foundation for modern ideas on the role of the tensor tympani in mammals. He was also the first to propose a non-auditory function to this middle ear muscle.</p>eng
dc.language.isoengeng
dc.publisherThe University of Bergeneng
dc.relation.haspart<p>Paper I: A morphologic study of Fluorogold-labeled tensor tympani motoneurons in mice. Sudeep Mukerji, Daniel J Lee & M. Christian Brown. Brain Research 2009; 1278:59-65 This article is not available in BORA. The published version is available at: <a href="http://dx.doi.org/10.1016/j.brainres.2009.04.035" target="blank">10.1016/j.brainres.2009.04.035</a> </p> <p>Paper II: Identification of inputs to olivocochlear neurons using transneuronal labeling with pseudorabies virus (PRV). M. Christian Brown, Sudeep Mukerji, Marie Drottar, Alanna Windsor & Daniel J Lee. Journal of the Association for Research in Otolaryngology 2013; 14:703-717 This article is not available in BORA. The published version is available at: <a href="http://dx.doi.org/10.1007/s10162-013-0400-5" target="blank">10.1007/s10162-013-0400-5</a> </p> <p>Paper III: De Visione, Voce et Auditu: the contribution of Hieronymous Fabricius to our understanding of tensor tympani function. Sudeep Mukerji & Daniel J Lee. Otolology & Neurotology 2010; 31:536-43 This article is not available in BORA. The published version is available at: <a href="http://dx.doi.org/10.1097/MAO.0b013e3181bc35b3" target="blank">10.1097/MAO.0b013e3181bc35b3</a> </p> <p>Paper IV: Auditory brainstem circuits mediating the middle ear muscle reflex. Sudeep Mukerji & Daniel J Lee. Trends in Amplification 2010; 14:170-191 This article is not available in BORA. The published version is available at: <a href="http://dx.doi.org/10.1177/1084713810381771" target="blank">10.1177/1084713810381771</a> </p>eng
dc.titleA transneuronal analysis of the olivocochlear and the middle ear muscle reflex pathwayseng
dc.typeDoctoral thesiseng
dc.rights.holderCopyright the author. All rights reserved.eng
bora.peerreviewedNot peer reviewedeng


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