Processing in the Cochlear Nucleus
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Pathophysiological Mechanisms and Functional Hearing Consequences of Auditory Neuropathy
doi:10.1093/brain/awv270 BRAIN 2015: 138; 3141–3158 | 3141 REVIEW ARTICLE Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy Gary Rance1 and Arnold Starr2 The effects of inner ear abnormality on audibility have been explored since the early 20th century when sound detection measures were first used to define and quantify ‘hearing loss’. The development in the 1970s of objective measures of cochlear hair cell Downloaded from function (cochlear microphonics, otoacoustic emissions, summating potentials) and auditory nerve/brainstem activity (auditory brainstem responses) have made it possible to distinguish both synaptic and auditory nerve disorders from sensory receptor loss. This distinction is critically important when considering aetiology and management. In this review we address the clinical and pathophysiological features of auditory neuropathy that distinguish site(s) of dysfunction. We describe the diagnostic criteria for: (i) presynaptic disorders affecting inner hair cells and ribbon synapses; (ii) postsynaptic disorders affecting unmyelinated auditory http://brain.oxfordjournals.org/ nerve dendrites; (iii) postsynaptic disorders affecting auditory ganglion cells and their myelinated axons and dendrites; and (iv) central neural pathway disorders affecting the auditory brainstem. We review data and principles to identify treatment options for affected patients and explore their benefits as a function of site of lesion. 1 Department of Audiology and Speech Pathology, The University of Melbourne, -
Projections from the Trigeminal Nuclear Complex to the Cochlear Nuclei: a Retrograde and Anterograde Tracing Study in the Guinea Pig
Journal of Neuroscience Research 78:901–907 (2004) Projections From the Trigeminal Nuclear Complex to the Cochlear Nuclei: a Retrograde and Anterograde Tracing Study in the Guinea Pig Jianxun Zhou and Susan Shore* Department of Otolaryngology and Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan In addition to input from auditory centers, the cochlear cuneate nucleus innervation of cochlear nucleus has been nucleus (CN) receives inputs from nonauditory centers, hypothesized to convey information about head and pinna including the trigeminal sensory complex. The detailed position for the purpose of localizing a sound source in anatomy, however, and the functional implications of the space (Young et al., 1995). In addition, interactions be- nonauditory innervation of the auditory system are not tween somatosensory and auditory systems have been fully understood. We demonstrated previously that the linked increasingly to phantom sound perception, also trigeminal ganglion projects to CN, with terminal labeling known as tinnitus. This is demonstrated in the observa- most dense in the marginal cell area and secondarily in tions that injuries of the head and neck region can lead to the magnocellular area of the ventral cochlear nucleus the onset of tinnitus in patients with no hearing loss (VCN). We continue this line of study by investigating the (Lockwood et al., 1998). projection from the spinal trigeminal nucleus to CN in We demonstrated previously projections from the guinea pig. After injections of the retrograde tracers Flu- trigeminal ganglion to CN in guinea pigs (Shore et al., oroGold or biotinylated dextran amine (BDA) in VCN, 2000). Terminal labeling of trigeminal ganglion projec- labeled cells were found in the spinal trigeminal nuclei, tions to the CN was found to be most dense in the most densely in the pars interpolaris and pars caudalis marginal cell area and secondarily in the magnocellular with ipsilateral dominance. -
Multisensory Integration in the Dorsal Cochlear Nucleus: Unit Responses to Acoustic and Trigeminal Ganglion Stimulation
European Journal of Neuroscience, Vol. 21, pp. 3334–3348, 2005 ª Federation of European Neuroscience Societies Multisensory integration in the dorsal cochlear nucleus: unit responses to acoustic and trigeminal ganglion stimulation S. E. Shore Kresge Hearing Research Institute and Department of Otolaryngology, University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109, USA Keywords: auditory, guinea pig, multisensory, neural pathways, somatosensory, trigeminal Abstract A necessary requirement for multisensory integration is the convergence of pathways from different senses. The dorsal cochlear nucleus (DCN) receives auditory input directly via the VIIIth nerve and somatosensory input indirectly from the Vth nerve via granule cells. Multisensory integration may occur in DCN cells that receive both trigeminal and auditory nerve input, such as the fusiform cell. We investigated trigeminal system influences on guinea pig DCN cells by stimulating the trigeminal ganglion while recording spontaneous and sound-driven activity from DCN neurons. A bipolar stimulating electrode was placed into the trigeminal ganglion of anesthetized guinea pigs using stereotaxic co-ordinates. Electrical stimuli were applied as bipolar pulses (100 ls per phase) with amplitudes ranging from 10 to 100 lA. Responses from DCN units were obtained using a 16-channel, four-shank electrode. Current pulses were presented alone or preceding 100- or 200-ms broadband noise (BBN) bursts. Thirty percent of DCN units showed either excitatory, inhibitory or excitatory–inhibitory responses to trigeminal ganglion stimulation. When paired with BBN stimulation, trigeminal stimulation suppressed or facilitated the firing rate in response to BBN in 78% of units, reflecting multisensory integration. Pulses preceding the acoustic stimuli by as much as 95 ms were able to alter responses to BBN. -
Direct Projections from Cochlear Nuclear Complex to Auditory Thalamus in the Rat
The Journal of Neuroscience, December 15, 2002, 22(24):10891–10897 Direct Projections from Cochlear Nuclear Complex to Auditory Thalamus in the Rat Manuel S. Malmierca,1 Miguel A. Mercha´n,1 Craig K. Henkel,2 and Douglas L. Oliver3 1Laboratory for the Neurobiology of Hearing, Institute for Neuroscience of Castilla y Leo´ n and Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain, 2Wake Forest University School of Medicine, Department of Neurobiology and Anatomy, Winston-Salem, North Carolina 27157-1010, and 3University of Connecticut Health Center, Department of Neuroscience, Farmington, Connecticut 06030-3401 It is known that the dorsal cochlear nucleus and medial genic- inferior colliculus and are widely distributed within the medial ulate body in the auditory system receive significant inputs from division of the medial geniculate, suggesting that the projection somatosensory and visual–motor sources, but the purpose of is not topographic. As a nonlemniscal auditory pathway that such inputs is not totally understood. Moreover, a direct con- parallels the conventional auditory lemniscal pathway, its func- nection of these structures has not been demonstrated, be- tions may be distinct from the perception of sound. Because cause it is generally accepted that the inferior colliculus is an this pathway links the parts of the auditory system with prom- obligatory relay for all ascending input. In the present study, we inent nonauditory, multimodal inputs, it may form a neural have used auditory neurophysiology, double labeling with an- network through which nonauditory sensory and visual–motor terograde tracers, and retrograde tracers to investigate the systems may modulate auditory information processing. -
Auditory and Vestibular Systems Objective • to Learn the Functional
Auditory and Vestibular Systems Objective • To learn the functional organization of the auditory and vestibular systems • To understand how one can use changes in auditory function following injury to localize the site of a lesion • To begin to learn the vestibular pathways, as a prelude to studying motor pathways controlling balance in a later lab. Ch 7 Key Figs: 7-1; 7-2; 7-4; 7-5 Clinical Case #2 Hearing loss and dizziness; CC4-1 Self evaluation • Be able to identify all structures listed in key terms and describe briefly their principal functions • Use neuroanatomy on the web to test your understanding ************************************************************************************** List of media F-5 Vestibular efferent connections The first order neurons of the vestibular system are bipolar cells whose cell bodies are located in the vestibular ganglion in the internal ear (NTA Fig. 7-3). The distal processes of these cells contact the receptor hair cells located within the ampulae of the semicircular canals and the utricle and saccule. The central processes of the bipolar cells constitute the vestibular portion of the vestibulocochlear (VIIIth cranial) nerve. Most of these primary vestibular afferents enter the ipsilateral brain stem inferior to the inferior cerebellar peduncle to terminate in the vestibular nuclear complex, which is located in the medulla and caudal pons. The vestibular nuclear complex (NTA Figs, 7-2, 7-3), which lies in the floor of the fourth ventricle, contains four nuclei: 1) the superior vestibular nucleus; 2) the inferior vestibular nucleus; 3) the lateral vestibular nucleus; and 4) the medial vestibular nucleus. Vestibular nuclei give rise to secondary fibers that project to the cerebellum, certain motor cranial nerve nuclei, the reticular formation, all spinal levels, and the thalamus. -
Anatomy of the Superior Olivary Complex.Pdf
Douglas Oliver University of Connecticut Health Center SUPERIOR OLIVE Auditory Pathways Auditory CORTEX GLUT Cortex GABA GLY Medial Geniculate MGB Body Inferior IC Colliculus DLL DLL COCHLEA VLL VLL DCN VCN SOC Auditory Pathways IC Organization of Superior Olivary Complex . Subdivisions and Cytoarchitecture . Neuron types . Inputs . Outputs . Synapses . Basic Circuit Cytoarchitecture of Superior Olivary Complex LSO LSO MSO MSO MNTB D MNTB M (somata & dendrites) (axons & endings) Tsuchitani, 1978, Fig. 10 Comparative anatomy of SOC Tetsufumi Ito & Shig Kuwada Binaural Basic Circuits 8 ‐ 9 Brodal Fig MSO: medial superior olive; LSO: lateral superior olive NTB: nucleus of trapezoid body; IC: inferior colliculus MSO Principle glutamate Cells . Fusiform . Bipolar . Disc‐shaped . Each dendrite innervated by a different side MSO‐In situ hybridization RPO MSO MNTB SPO LSO VGLUT1 VGLUT2 VIAAT NISSL MSO Inputs and Synapses H=high frequency EI - ILD L=low frequency EE - ITD LSO MSO L L B H B B H G LNTB TO LSO MNTB E=Excitation (glutamate) ‐‐‐ I=Inhibition (glycine) ITD CODING Unlike retinal targets, the cochlear nuclei contain maps of frequency, not location. So how does the auditory system know ‘where’ a sound is coming from? T + ITD T By comparing the interaural time differences (ITD) between the ears How is this accomplished?... LSO MSO Right Input A Right Input B C Time Code Time Code E E A A B B C C D D E E Output Output abcde Place Code abcde Place Code Excitation MSO creates a response to Left Input Left Input Inhibition interaural time differences I Time Code E Time Code DEMSO "peak" unit LSO "trough" unit ITD ITD Figure 14.2 Binaural Responses in MSO MSO Summary . -
The Superior Olivary Complex +
Excitatory and inhibitory transmission in the superior olivary complex. Ian D. Forsythe, Matt Barker, Margaret Barnes-Davies, Brian Billups, Paul Dodson, Fatima Osmani, Steven Owens and Adrian Wong. Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN. UK. The timing and pattern of action potentials propagating into the brainstem from both cochleae contain information about the azimuth location of that sound in auditory space. This binaural information is integrated in the superior olivary complex. This part of the auditory pathway is adapted for fast conduction speeds and the preservation of timing information with several complimentary mechanisms (see Oertel, 1999; Trussell, 1999). There are large diameter axons terminating in giant somatic synapses that activate receptor ion channels with fast kinetics. The resultant postsynaptic potentials generated in the receiving neuron are integrated with a suite of voltage-gated ion channels that determine the action potential threshold, duration and repetitive firing properties. We have studied presynaptic and postsynaptic mechanisms that regulate efficacy, timing and integration of synaptic responses in the medial nucleus of the trapezoid body and the medial and lateral superior olives. Presynaptic calcium currents in the calyx of Held. The calyx of Held is a giant synaptic terminal that forms around the soma of principal cells in the Medial Nucleus of the Trapezoid Body (MNTB) (Forsythe, 1994). Each MNTB neuron receives a single calyx. Action potentials propagating into the synaptic terminal trigger the opening of P-type calcium channels (Forsythe et al. 1998) which in turn trigger the release of glutamate into the synaptic cleft (Borst et al., 1995). -
Use of Calcium-Binding Proteins to Map Inputs in Vestibular Nuclei of the Gerbil
THE JOURNAL OF COMPARATIVE NEUROLOGY 386:317–327 (1997) Use of Calcium-Binding Proteins to Map Inputs in Vestibular Nuclei of the Gerbil GOLDA ANNE KEVETTER* AND ROBERT B. LEONARD Departments of Otolaryngology, Anatomy and Neurosciences, and Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555 ABSTRACT We wished to determine whether calbindin and/or calretinin are appropriate markers for vestibular afferents, a population of neurons in the vestibular nuclear complex, or cerebellar Purkinje inputs. To accomplish this goal, immunocytochemical staining was observed in gerbils after lesions of the vestibular nerve central to the ganglion, the cerebellum, or both. Eleven to fourteen days after recovery, the brain was processed for immunocytochemical identification of calretinin and calbindin. After lesion of the vestibular nerve, no calretinin staining was seen in any of the vestibular nuclei except for a population of intrinsic neurons, which showed no obvious change in number or staining pattern. Calbindin staining was reduced in all nuclei except the dorsal part of the lateral vestibular nuclei. The density of staining of each marker, measured in the magnocellular medial vestibular nucleus, was signifi- cantly reduced. After the cerebellar lesion, no differences in calretinin staining were noted. However, calbindin staining was greatly reduced in all nuclei. The density of staining, measured in the caudal medial vestibular nucleus, was significantly lower. After a combined lesion of the cerebellum and vestibular nerve, the distribution and density of calretinin staining resembled that after vestibular nerve section alone, whereas calbindin staining was no longer seen. This study demonstrates that calretinin and calbindin are effective markers for the identification of vestibular afferents. -
Selective Degeneration of Synapses in the Dorsal Cochlear Nucleus of Chinchilla Following Acoustic Trauma and Effects of Antioxidant Treatment
Hearing Research 283 (2012) 1e13 Contents lists available at SciVerse ScienceDirect Hearing Research journal homepage: www.elsevier.com/locate/heares Research paper Selective degeneration of synapses in the dorsal cochlear nucleus of chinchilla following acoustic trauma and effects of antioxidant treatment Xiaoping Du a, Kejian Chen a,1, Chul-Hee Choi a,2, Wei Li a, Weihua Cheng a, Charles Stewart a,b, Ning Hu a, Robert A. Floyd b, Richard D. Kopke a,c,d,* a Hough Ear Institute, Oklahoma, OK 73112, USA b Experimental Therapeutic Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK 73104, USA c Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA d Department of Otolaryngology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA article info abstract Article history: The purpose of this study was to reveal synaptic plasticity within the dorsal cochlear nucleus (DCN) as Received 31 May 2011 a result of noise trauma and to determine whether effective antioxidant protection to the cochlea can Received in revised form also impact plasticity changes in the DCN. Expression of synapse activity markers (synaptophysin and 18 November 2011 precerebellin) and ultrastructure of synapses were examined in the DCN of chinchilla 10 days after Accepted 30 November 2011 a 105 dB SPL octave-band noise (centered at 4 kHz, 6 h) exposure. One group of chinchilla was treated Available online 9 December 2011 with a combination of antioxidants (4-hydroxy phenyl N-tert-butylnitrone, N-acetyl-L-cysteine and acetyl-L-carnitine) beginning 4 h after noise exposure. Down-regulated synaptophysin and precerebellin expression, as well as selective degeneration of nerve terminals surrounding cartwheel cells and their primary dendrites were found in the fusiform soma layer in the middle region of the DCN of the noise exposure group. -
Cranial Nerve VIII
Cranial Nerve VIII Color Code Important (The Vestibulo-Cochlear Nerve) Doctors Notes Notes/Extra explanation Please view our Editing File before studying this lecture to check for any changes. Objectives At the end of the lecture, the students should be able to: ✓ List the nuclei related to vestibular and cochlear nerves in the brain stem. ✓ Describe the type and site of each nucleus. ✓ Describe the vestibular pathways and its main connections. ✓ Describe the auditory pathway and its main connections. Due to the difference of arrangement of the lecture between the girls and boys slides we will stick to the girls slides then summarize the pathway according to the boys slides. Ponto-medullary Sulcus (cerebello- pontine angle) Recall: both cranial nerves 8 and 7 emerge from the ventral surface of the brainstem at the ponto- medullary sulcus (cerebello-pontine angle) Brain – Ventral Surface Vestibulo-Cochlear (VIII) 8th Cranial Nerve o Type: Special sensory (SSA) o Conveys impulses from inner ear to nervous system. o Components: • Vestibular part: conveys impulses associated with body posture ,balance and coordination of head & eye movements. • Cochlear part: conveys impulses associated with hearing. o Vestibular & cochlear parts leave the ventral surface* of brain stem through the pontomedullary sulcus ‘at cerebellopontine angle*’ (lateral to facial nerve), run laterally in posterior cranial fossa and enter the internal acoustic meatus along with 7th (facial) nerve. *see the previous slide Auditory Pathway Only on the girls’ slides 04:14 Characteristics: o It is a multisynaptic pathway o There are several locations between medulla and the thalamus where axons may synapse and not all the fibers behave in the same manner. -
Auditory Nerve.Pdf
1 Sound waves from the auditory environment all combine in the ear canal to form a complex waveform. This waveform is deconstructed by the cochlea with respect to time, loudness, and frequency and neural signals representing these features are carried into the brain by the auditory nerve. It is thought that features of the sounds are processed centrally along parallel and hierarchical pathways where eventually percepts of the sounds are organized. 2 In mammals, the neural representation of acoustic information enters the brain by way of the auditory nerve. The auditory nerve terminates in the cochlear nucleus, and the cochlear nucleus in turn gives rise to multiple output projections that form separate but parallel limbs of the ascending auditory pathways. How the brain normally processes acoustic information will be heavily dependent upon the organization of auditory nerve input to the cochlear nucleus and on the nature of the different neural circuits that are established at this early stage. 3 This histology slide of a cat cochlea (right) illustrates the sensory receptors, the auditory nerve, and its target the cochlear nucleus. The orientation of the cut is illustrated by the pink line in the drawing of the cat head (left). We learned about the relationship between these structures by inserting a dye-filled micropipette into the auditory nerve and making small injections of the dye. After histological processing, stained single fibers were reconstruct back to their origin, and traced centrally to determine how they terminated in the brain. We will review the components of the nerve with respect to composition, innervation of the receptors, cell body morphology, myelination, and central terminations. -
Anatomy of the Ear ANATOMY & Glossary of Terms
Anatomy of the Ear ANATOMY & Glossary of Terms By Vestibular Disorders Association HEARING & ANATOMY BALANCE The human inner ear contains two divisions: the hearing (auditory) The human ear contains component—the cochlea, and a balance (vestibular) component—the two components: auditory peripheral vestibular system. Peripheral in this context refers to (cochlea) & balance a system that is outside of the central nervous system (brain and (vestibular). brainstem). The peripheral vestibular system sends information to the brain and brainstem. The vestibular system in each ear consists of a complex series of passageways and chambers within the bony skull. Within these ARTICLE passageways are tubes (semicircular canals), and sacs (a utricle and saccule), filled with a fluid called endolymph. Around the outside of the tubes and sacs is a different fluid called perilymph. Both of these fluids are of precise chemical compositions, and they are different. The mechanism that regulates the amount and composition of these fluids is 04 important to the proper functioning of the inner ear. Each of the semicircular canals is located in a different spatial plane. They are located at right angles to each other and to those in the ear on the opposite side of the head. At the base of each canal is a swelling DID THIS ARTICLE (ampulla) and within each ampulla is a sensory receptor (cupula). HELP YOU? MOVEMENT AND BALANCE SUPPORT VEDA @ VESTIBULAR.ORG With head movement in the plane or angle in which a canal is positioned, the endo-lymphatic fluid within that canal, because of inertia, lags behind. When this fluid lags behind, the sensory receptor within the canal is bent.