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Cerebellum (London, England) Oct 2015Although the major emphasis of Enrico Mugnaini's research has been on investigations of the cerebellum, a significant amount of work over a relatively short span of time... (Review)
Review
Although the major emphasis of Enrico Mugnaini's research has been on investigations of the cerebellum, a significant amount of work over a relatively short span of time was also done in his lab on a number of other brain systems. These centered on sensory systems. One of these extra-cerebellar systems that he embraced was the auditory system. Portions of the cochlear nucleus, the first synaptic relay station along the central auditory pathways, possess a cerebellar-like circuitry and neurochemistry, and this no doubt lured Enrico into the auditory field. As new tools became available to pursue neuroanatomical research in general, which included a novel antibody to glutamic acid decarboxylase (GAD), Enrico's lab soon branched out into investigating many other brain structures beyond the cerebellum, with an overall goal of producing a map illustrating GAD expression in the brain. In collaboration with long-term colleagues, one of these many non-cerebellar regions he took an interest in was an efferent pathway originating in the superior olive and projecting to the cochlea, the peripheral end organ for hearing. There was a need for a more complete neurochemical map of this olivocochlear efferent system, and armed with new antibodies and well-established tract tracing tools, together we set out to further explore this system. This short review describes the work done with Enrico on the olivocochlear system of rodents, and also continues the story beyond Enrico's lab to reveal how the work done in his lab fits into the larger scheme of current, ongoing research into the olivocochlear system.
Topics: Animals; Auditory Pathways; Cerebellum; History, 20th Century; Humans; Mammals; Neuroanatomy; Neurochemistry; Olivary Nucleus
PubMed: 25592068
DOI: 10.1007/s12311-014-0637-5 -
Epilepsy & Behavior : E&B Jun 2017The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic-clonic seizures induced by external... (Review)
Review
The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic-clonic seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
Topics: Acoustic Stimulation; Animals; Auditory Threshold; Brain Stem; Cochlea; Cricetinae; Disease Models, Animal; Epilepsy, Reflex; Mesocricetus; Olivary Nucleus; Otoacoustic Emissions, Spontaneous; Seizures
PubMed: 27492627
DOI: 10.1016/j.yebeh.2016.05.040 -
Progress in Brain Research 1997Motor control is defined as the process of restricting the output of the motor nervous system so that meaningful and coordinated behavior ensues. The high dimensionality... (Review)
Review
Motor control is defined as the process of restricting the output of the motor nervous system so that meaningful and coordinated behavior ensues. The high dimensionality of the computation underlying motor control is presented and a simplifying framework is outlined. Evidence that movements are performed non-continuously is reviewed as is the construct of the 'motor synergy' as a fundamental unit of control. It is proposed that the pulsatile nature of movement and the tendency of muscle collectives to be activated as synergies reflect processes that the nervous system has evolved to reduce the dimensionality of motor control. We propose that the inferior olive simplifies the computation underlying motor control by biasing the activities of spinal and cranial motor systems so that discrete collectives of muscles are predisposed to contract at specific times during movement. The well-characterized oscillatory activity of olivary neurons is postulated to provide a pacemaking signal and to restrict the control process to particular moments in time while the process of electrotonic coupling and uncoupling of assemblies of olivary neurons is proposed to underlie the spatial distribution of synergic muscle activations. It is proposed that the olivocerebellar contribution to the control process is to allow movements to be executed rapidly in a feedforward manner, so that the need for sensory guidance and feedback is minimized.
Topics: Animals; Cerebellum; Humans; Models, Neurological; Motor Activity; Movement; Muscle, Skeletal; Olivary Nucleus; Spinal Cord
PubMed: 9193160
DOI: 10.1016/s0079-6123(08)63380-4 -
Brain, Behavior and Evolution 2012The arcuate nucleus is a prominent cell group in the human hindbrain, characterized by its position on the pial surface of the pyramid. It is considered to be a...
The arcuate nucleus is a prominent cell group in the human hindbrain, characterized by its position on the pial surface of the pyramid. It is considered to be a precerebellar nucleus and has been implicated in the pathology of several disorders of respiration. An arcuate nucleus has not been convincingly demonstrated in other mammals, but we have found a similarly positioned nucleus in the C57BL/6J mouse. The mouse arcuate nucleus consists of a variable group of neurons lying on the pial surface of the pyramid. The nucleus is continuous with the ventrolateral part of the principal nucleus of the inferior olive and both groups are calbindin positive. At first we thought that this mouse nucleus was homologous with the human arcuate nucleus, but we have discovered that the neurons of the human nucleus are calbindin negative, and are therefore not olivary in nature. We have compared the mouse arcuate neurons with those of the inferior olive in terms of molecular markers and cerebellar projection. The neurons of the arcuate nucleus and of the inferior olive share three major characteristics: they both contain neurons utilizing glutamate, serotonin or acetylcholine as neurotransmitters; they both project to the contralateral cerebellum, and they both express a number of genes not present in the major mossy fiber issuing precerebellar nuclei. Most importantly, both cell groups express calbindin in an area of the ventral hindbrain almost completely devoid of calbindin-positive cells. We conclude that the neurons of the hindbrain mouse arcuate nucleus are a displaced part of the inferior olive, possibly separated by the caudal growth of the pyramidal tract during development. The arcuate nucleus reported in the C57BL/6J mouse can therefore be regarded as a subgroup of the rostral inferior olive, closely allied with the ventral tier of the principal nucleus.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Biomarkers; Calbindins; Cholinergic Neurons; Glutamic Acid; Humans; Mice; Mice, Inbred C57BL; Molecular Imaging; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neurons; Olivary Nucleus; S100 Calcium Binding Protein G; Serotonergic Neurons
PubMed: 22301572
DOI: 10.1159/000335032 -
Neuron Aug 2017Ca-activated ion channels shape membrane excitability and Ca dynamics in response to cytoplasmic Ca elevation. Compared to the Ca-activated K channels, known as BK and...
Ca-activated ion channels shape membrane excitability and Ca dynamics in response to cytoplasmic Ca elevation. Compared to the Ca-activated K channels, known as BK and SK channels, the physiological importance of Ca-activated Cl channels (CaCCs) in neurons has been largely overlooked. Here we report that CaCCs coexist with BK and SK channels in inferior olivary (IO) neurons that send climbing fibers to innervate cerebellar Purkinje cells for the control of motor learning and timing. Ca influx through the dendritic high-threshold voltage-gated Ca channels activates CaCCs, which contribute to membrane repolarization of IO neurons. Loss of TMEM16B expression resulted in the absence of CaCCs in IO neurons, leading to markedly diminished action potential firing of IO neurons in TMEM16B knockout mice. Moreover, these mutant mice exhibited severe cerebellar motor learning deficits. Our findings thus advance the understanding of the neurophysiology of CaCCs and the ionic basis of IO neuron excitability.
Topics: Action Potentials; Animals; Anoctamins; Calcium; Cerebellum; Chloride Channels; Learning; Learning Disabilities; Mice; Mice, Knockout; Motor Skills; Neurons; Olivary Nucleus; Purkinje Cells
PubMed: 28858616
DOI: 10.1016/j.neuron.2017.08.010 -
Journal of Integrative Neuroscience Sep 2020Transsynaptic degeneration in the cerebellum and brainstem may give rise to a rare neurological condition with various clinical manifestations, namely hypertrophic... (Meta-Analysis)
Meta-Analysis
Transsynaptic degeneration in the cerebellum and brainstem may give rise to a rare neurological condition with various clinical manifestations, namely hypertrophic olivary degeneration. The classical manifestations of hypertrophic olivary degeneration comprise myoclonus, palatal tremor, ataxia, and ocular symptoms. Any lesions interrupting the dentate-rubro-olivary pathway, referred to as the anatomic Guillain-Mollaret triangle, contribute to the broad aetiologies of hypertrophic olivary degeneration. The clinical diagnosis depends primarily on the associated symptoms and the characteristic magnetic resonance imaging findings. Concerning treatment and prognosis, there are no widely accepted guidelines. Here, we identified 11 cases of hypertrophic olivary degeneration secondary to brainstem infarction from 1964 to the present. Combined with two of our cases, the clinical and imaging findings of 13 patients with hypertrophic olivary degeneration secondary to brainstem infarction were studied. A meta-analysis of case studies gives the correlation coefficient between infraction location and time to develop hypertrophic olivary degeneration as 0.217 ( = 0.393, > 0.05). At the significance level of < 0.05, there was no significant correlation between information location and time to develop hyperophic olivary degeneration. The χ between infraction location and magnetic resonance imaging findings of hypertrophic olivary degeneration was 8.750 ( = 0.364, > 0.05). At the significance level of < 0.05, there was no significant correlation between infraction location and magnetic resonance imaging findings of hypertrophic olivary degeneration. Conclusion based on the analysis of available data suggests that when newly developed or progressive worsening motor symptoms are presented in patients with previous brainstem infarction, a diagnosis of hypertrophic olivary degeneration should be investigated.
Topics: Adult; Aged; Brain Stem Infarctions; Female; Humans; Hypertrophy; Male; Middle Aged; Neurodegenerative Diseases; Olivary Nucleus
PubMed: 33070531
DOI: 10.31083/j.jin.2020.03.1238 -
The Journal of Comparative Neurology Apr 2000A neural connection between the trigeminal ganglion and the auditory brainstem was investigated by using retrograde and anterograde tract tracing methods: iontophoretic...
A neural connection between the trigeminal ganglion and the auditory brainstem was investigated by using retrograde and anterograde tract tracing methods: iontophoretic injections of biocytin or biotinylated dextran-amine (BDA) were made into the guinea pig trigeminal ganglion, and anterograde labeling was examined in the cochlear nucleus and superior olivary complex. Terminal labeling after biocytin and BDA injections into the ganglion was found to be most dense in the marginal cell area and secondarily in the magnocellular area of the ventral cochlear nucleus (VCN). Anterograde and retrograde labeling was also seen in the shell regions of the lateral superior olivary complex and in periolivary regions. The labeling was seen in the neuropil, on neuronal somata, and in regions surrounding blood vessels. Retrograde labeling was investigated using either wheatgerm agglutinin-horseradish peroxidase (WGA-HRP), BDA, or a fluorescent tracer, iontophoretically injected into the VCN. Cells filled by retrograde labeling were found in the ophthalmic and mandibular divisions of the trigeminal ganglion. We have previously shown that these divisions project to the cochlea and middle ear, respectively. This study provides the first evidence that the trigeminal ganglion innervates the cochlear nucleus and superior olivary complex. This projection from a predominantly somatosensory ganglion may be related to integration mechanisms involving the auditory end organ and its central targets.
Topics: Animals; Auditory Pathways; Brain Mapping; Brain Stem; Cochlear Nucleus; Female; Guinea Pigs; Olivary Nucleus; Pregnancy; Trigeminal Ganglion; Trigeminal Nuclei
PubMed: 10723004
DOI: 10.1002/(sici)1096-9861(20000410)419:3<271::aid-cne1>3.0.co;2-m -
The Journal of Comparative Neurology Jun 2010Three nuclei of the lateral lemniscus are present in the zebra finch, ventral (LLV), intermediate (LLI), and dorsal (LLD). LLV is separate from the superior olive (OS):...
Connections of the auditory brainstem in a songbird, Taeniopygia guttata. II. Projections of nucleus angularis and nucleus laminaris to the superior olive and lateral lemniscal nuclei.
Three nuclei of the lateral lemniscus are present in the zebra finch, ventral (LLV), intermediate (LLI), and dorsal (LLD). LLV is separate from the superior olive (OS): it lies closer to the spinal lemniscus and extends much further rostrally around the pontine periphery. LLI extends from a caudal position ventrolateral to the principal sensory trigeminal nucleus (LLIc) to a rostral position medial to the ventrolateral parabrachial nucleus (LLIr). LLD consists of posterior (LLDp) and anterior (LLDa) parts, which are largely coextensive rostrocaudally, although LLDa lies medial to LLDp. All nuclei are identifiable on the basis of cytochrome oxidase activity. The cochlear nucleus angularis (NA) and the third-order nucleus laminaris (NL) project on OS predominantly ipsilaterally, on LLV and LLI predominantly contralaterally, and on LLD contralaterally only. The NA projections are heavier than those of NL and differ from them primarily in their terminations within LLD: NA projects to LLDp, whereas NL projects to LLDa. In this the projections are similar to those in the barn owl (Takahashi and Konishi [1988] J Comp Neurol 274:212-238), in which time and intensity pathways remain separate as far as the central nucleus of the inferior colliculus (MLd). In contrast, in the zebra finch, although NA and NL projections remain separate within LLD, the projections of LLDa and LLDp become intermixed within MLd (Wild et al., J Comp Neurol, this issue), consistent with the intermixing of the direct NA and NL projections to MLd (Krützfeldt et al., J Comp Neurol, this issue).
Topics: Animals; Auditory Pathways; Brain Stem; Cochlear Nucleus; Finches; Inferior Colliculi; Male; Olivary Nucleus; Staining and Labeling
PubMed: 20394062
DOI: 10.1002/cne.22324 -
Cerebellum (London, England) Aug 2013Clinicoanatomic correlation in the spinocerebellar ataxias (SCA) and Friedreich's ataxia (FRDA) is difficult as these diseases differentially affect multiple sites in...
Clinicoanatomic correlation in the spinocerebellar ataxias (SCA) and Friedreich's ataxia (FRDA) is difficult as these diseases differentially affect multiple sites in the central and peripheral nervous systems. A new way to study cerebellar ataxia is the systematic analysis of the "reciprocal cerebellar circuitry" that consists of tightly organized reciprocal connections between Purkinje cells, dentate nuclei (DN), and inferior olivary nuclei (ION). This circuitry is similar to but not identical with the "cerebellar module" in experimental animals. Neurohumoral transmitters operating in the circuitry are both inhibitory (γ-aminobutyric acid in corticonuclear and dentato-olivary fibers) and excitatory (glutamate in olivocerebellar or climbing fibers). Glutamatergic climbing fibers also issue collaterals to the DN. The present study applied five immunohistochemical markers in six types of SCA (1, 2, 3, 6, 7, 17), genetically undefined SCA, FRDA, and FRDA carriers to identify interruptions within the circuitry: calbindin-D28k, neuron-specific enolase, glutamic acid decarboxylase, and vesicular glutamate transporters 1 and 2. Lesions of the cerebellar cortex, DN, and ION were scored according to a guide as 0 (normal), 1 (mild), 2 (moderate), and 3 (severe). Results of each of the five immunohistochemical stains were examined separately for each of the three regions. Combining scores of each anatomical region and each stain yielded a total score as an indicator of pathological severity. Total scores ranged from 16 to 38 in SCA-1 (nine cases); 22 to 39 in SCA-2 (six cases); 9 to 15 in SCA-3 (four cases); and 13 and 25 in SCA-6 (two cases). In single cases of SCA-7 and SCA-17, scores were 16 and 31, respectively. In two genetically undefined SCA, scores were 36 and 37, respectively. In nine cases of FRDA, total scores ranged from 11 to 19. The low scores in SCA-3 and FRDA reflect selective atrophy of the DN. The FRDA carriers did not differ from normal controls. These observations offer a semiquantitative assessment of the critical role of the DN in the ataxic phenotype of SCA and FRDA while other parts of the circuitry appear less important.
Topics: Cerebellar Nuclei; Cerebellum; Humans; Nerve Net; Olivary Nucleus; Spinocerebellar Degenerations
PubMed: 23389921
DOI: 10.1007/s12311-013-0456-0 -
Hearing Research May 2018The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC... (Review)
Review
The anatomy and physiology of olivocochlear (OC) efferents are reviewed. To help interpret these, recent advances in cochlear mechanics are also reviewed. Lateral OC (LOC) efferents innervate primary auditory-nerve (AN) fiber dendrites. The most important LOC function may be to reduce auditory neuropathy. Medial OC (MOC) efferents innervate the outer hair cells (OHCs) and act to turn down the gain of cochlear amplification. Cochlear amplification had been thought to act only through basilar membrane (BM) motion, but recent reports show that motion near the reticular lamina (RL) is amplified more than BM motion, and that RL-motion amplification extends to several octaves below the local characteristic frequency. Data on efferent effects on AN-fiber responses, otoacoustic emissions (OAEs) and human psychophysics are reviewed and reinterpreted in the light of the new cochlear-mechanical data. The possible origin of OAEs in RL motion is considered. MOC-effect measuring methods and MOC-induced changes in human responses are also reviewed, including that ipsilateral and contralateral sound can produce MOC effects with different patterns across frequency. MOC efferents help to reduce damage due to acoustic trauma. Many, but not all, reports show that subjects with stronger contralaterally-evoked MOC effects have better ability to detect signals (e.g. speech) in noise, and that MOC effects can be modulated by attention.
Topics: Acoustic Stimulation; Animals; Attention; Auditory Perception; Cochlea; Cochlear Nerve; Efferent Pathways; Hearing; Humans; Mechanotransduction, Cellular; Noise; Olivary Nucleus; Perceptual Masking; Signal Detection, Psychological; Speech Perception
PubMed: 29291948
DOI: 10.1016/j.heares.2017.12.012