-
The Journal of Comparative Neurology Oct 2019Descending auditory pathways can modify afferent auditory input en route to cortex. One component of these pathways is the olivocochlear system which originates in...
Descending auditory pathways can modify afferent auditory input en route to cortex. One component of these pathways is the olivocochlear system which originates in brainstem and terminates in cochlea. Medial olivocochlear (MOC) neurons also project collaterals to cochlear nucleus and make synaptic contacts with dendrites of multipolar neurons. Two broadly distinct populations of multipolar cells exist: T-stellate and D-stellate neurons, thought to project to inferior colliculus and contralateral cochlear nucleus, respectively. It is unclear which of these neurons receive direct MOC collateral input due to conflicting results between in vivo and in vitro studies. This study used anatomical techniques to identify which multipolar cell population receives synaptic innervation from MOC collaterals. The retrograde tracer Fluorogold was injected into inferior colliculus or cochlear nucleus to label T-stellate and D-stellate neurons, respectively. Axonal branches of MOC neurons were labeled by biocytin injections at the floor of the fourth ventricle. Fluorogold injections resulted in labeled cochlear nucleus multipolar neurons. Biocytin abundantly labeled MOC collaterals which entered cochlear nucleus. Microscopic analysis revealed that MOC collaterals made some putative synaptic contacts with the retrogradely labeled neurons but many more putative contacts were observed on unidentified neural targets. This suggest that both T- and D-stellate neurons receive synaptic innervation from the MOC collaterals on their somata and proximal dendrites. The prevalence of these contacts cannot be stated with certainty because of technical limitations, but the possibility exists that the collaterals may also make contacts with neurons not projecting to inferior colliculus or the contralateral cochlear nucleus.
Topics: Animals; Auditory Pathways; Cochlear Nucleus; Female; Guinea Pigs; Male; Olivary Nucleus; Rats; Rats, Wistar; Species Specificity
PubMed: 30861121
DOI: 10.1002/cne.24681 -
Journal of the Neurological Sciences Nov 2016Hypertrophic Olivary Degeneration (HOD) is a rare neurological condition caused by trans-synaptic degeneration in the brainstem and cerebellum, resulting in varied... (Review)
Review
Hypertrophic Olivary Degeneration (HOD) is a rare neurological condition caused by trans-synaptic degeneration in the brainstem and cerebellum, resulting in varied clinical symptoms, classical being palatal tremors, along with characteristic imaging presentation. Large number of pathologic lesions can cause this condition, ranging from ischemic stroke to neoplasm. The most common conditions include hemorrhage, vascular malformations and infarct. Magnetic resonance scan (MRI) is the imaging modality of choice which shows signal changes with hypertrophy of the inferior olivary nucleus, as well as the primary underlying pathology. Through this pictorial essay, we present the imaging and clinical findings in a number of patients with HOD secondary to varied causes and explain the mechanism behind the changes.
Topics: Adult; Aged; Diagnosis, Differential; Female; Humans; Hypertrophy; Male; Middle Aged; Neurodegenerative Diseases; Olivary Nucleus
PubMed: 27772756
DOI: 10.1016/j.jns.2016.09.055 -
American Journal of Physiology.... May 2016The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin...
The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated.
Topics: Aged; Aged, 80 and over; Antibodies; Autoradiography; Cohort Studies; Gene Expression Regulation; Humans; Medulla Oblongata; Radioligand Assay; Receptors, Calcitonin
PubMed: 26911465
DOI: 10.1152/ajpregu.00539.2015 -
RNA Biology Jan 2023The peripheral and central auditory subsystems together form a complex sensory network that allows an organism to hear. The genetic programs of the two subsystems must...
The peripheral and central auditory subsystems together form a complex sensory network that allows an organism to hear. The genetic programs of the two subsystems must therefore be tightly coordinated during development. Yet, their interactions and common expression pathways have never been systematically explored. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and are essential for normal development of the auditory system. We performed mRNA and small-RNA sequencing of organs from both auditory subsystems at three critical developmental timepoints (E16, P0, P16) to obtain a comprehensive and unbiased insight of their expression profiles. Our analysis reveals common and organ-specific expression patterns for differentially regulated mRNAs and miRNAs, which could be clustered with a particular selection of functions such as inner ear development, Wnt signalling, K+ transport, and axon guidance, based on gene ontology. Bioinformatics detected enrichment of predicted targets of specific miRNAs in the clusters and predicted regulatory interactions by monitoring opposite trends of expression of miRNAs and their targets. This approach identified six miRNAs as strong regulatory candidates for both subsystems. Among them was miR-96, an established critical factor for proper development in both subsystems, demonstrating the strength of our approach. We suggest that other miRNAs identified by this analysis are also common effectors of proper hearing acquirement. This first combined comprehensive analysis of the developmental program of the peripheral and central auditory systems provides important data and bioinformatics insights into the shared genetic program of the two sensory subsystems and their regulation by miRNAs.
Topics: Superior Olivary Complex; Cochlea; Computational Biology; Gene Ontology; MicroRNAs; RNA, Messenger
PubMed: 37602850
DOI: 10.1080/15476286.2023.2247628 -
Brain Structure & Function Jan 2020The olivary pretectal nucleus is the first central connection in the pupillary light reflex pathway, the circuit that adjusts the diameter of the pupil in response to...
The olivary pretectal nucleus is the first central connection in the pupillary light reflex pathway, the circuit that adjusts the diameter of the pupil in response to ambient light levels. This study investigated aspects of the morphology and connectivity of the olivary pretectal nucleus in macaque monkeys by use of anterograde and retrograde tracers. Within the pretectum, the vast majority of neurons projecting to the preganglionic Edinger-Westphal nucleus were found within the olivary pretectal nucleus. Most of these neurons had somata located at the periphery of the nucleus and their heavily branched dendrites extended into the core of the nucleus. Retinal terminals were concentrated within the borders of the olivary pretectal nucleus. Ultrastructural examination of these terminals showed that they had clear spherical vesicles, occasional dense-core vesicles, and made asymmetric synaptic contacts. Retrogradely labeled cells projecting to the preganglionic Edinger-Westphal nucleus displayed relatively few somatic contacts. Double labeling indicated that these neurons receive direct retinal input. The concentration of retinal terminals within the nucleus and the extensive dendritic trees of the olivary projection cells provide a substrate for very large receptive fields. In some species, pretectal commissural connections are a substrate for balancing the direct and consensual pupillary responses to produce pupils of equal size. In the macaque, there was little evidence for such a commissural projection based on either anterograde or retrograde tracing. This may be due to the fact that each macaque retina provides nearly equal density projections to the ipsilateral and contralateral olivary pretectal nucleus.
Topics: Animals; Edinger-Westphal Nucleus; Female; Macaca fascicularis; Male; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neurons; Presynaptic Terminals; Pretectal Region; Reflex, Pupillary; Retina
PubMed: 31848686
DOI: 10.1007/s00429-019-02003-7 -
Hearing Research May 2019The auditory part of the brainstem is composed of several nuclei specialized in the computation of the different spectral and temporal features of the sound before it... (Review)
Review
The auditory part of the brainstem is composed of several nuclei specialized in the computation of the different spectral and temporal features of the sound before it reaches the higher auditory regions. There are a high diversity of neuronal types in these nuclei, many with remarkable electrophysiological and synaptic properties unique to these structures. This diversity reflects specializations necessary to process the different auditory signals in order to extract precisely the acoustic information necessary for the auditory perception by the animal. Low threshold Kv1 channels and HCN channels are expressed in neurons that use timing clues for auditory processing, like bushy and octopus cells, in order to restrict action potential firing and reduce input resistance and membrane time constant. Kv3 channels allow principal neurons of the MNTB and pyramidal DCN neurons to fire fast trains of action potentials. Calcium channels on cartwheel DCN neurons produce complex spikes characteristic of these neurons. Calyceal synapses compensate the low input resistance of bushy and principal neurons of the MNTB by releasing hundreds of glutamate vesicles resulting in large EPSCs acting in fast ionotropic glutamate receptors, in order to reduce temporal summation of synaptic potentials, allowing more precise correspondence of pre- and post-synaptic potentials, and phase-locking. Pre-synaptic calyceal sodium channels have fast recovery from inactivation allowing extremely fast trains of action potential firing, and persistent sodium channels produce spontaneous activity of fusiform neurons at rest, which expands the dynamic range of these neurons. The unique combinations of different ion channels, ionotropic receptors and synaptic structures create a unique functional diversity of neurons extremely adapted to their complex functions in the auditory processing.
Topics: Animals; Auditory Pathways; Brain Stem; Cochlear Nerve; Cochlear Nucleus; Humans; Ion Channels; Mammals; Models, Neurological; Neurons; Superior Olivary Complex; Synapses
PubMed: 30606624
DOI: 10.1016/j.heares.2018.12.011 -
The Indian Journal of Radiology &... 2019Hypertrophic olivary degeneration is a rare occurrence in which different pathological processes including enlargement and vacuolation of the neurons, demyelination of...
Hypertrophic olivary degeneration is a rare occurrence in which different pathological processes including enlargement and vacuolation of the neurons, demyelination of the white matter, and fibrillary gliosis of the inferior olivary nucleus take place. It mostly develops secondary to a destructive lesion involving the Guillain-Mollaret pathway. The mostly reported destructive lesions causing hypertrophic olivary degeneration are stroke, trauma, tumors, neurosurgical interventions, and gamma knife treatment of brainstem cavernoma. It presents with symptomatic palatal tremor, and typically appears as an expansive nonenhancing nodular lesion that shows increased signal intensity on magnetic resonance imaging (MRI). The identification of hypertrophic olivary degeneration on MRI is of great importance as its MRI appearance is very similar to those of more severe pathologies, including tumors, infarction, demyelinating lesions, and infections. We present a case of hypertrophic olivary degeneration in a patient with a history of ischemic stroke two years before the development of palatal tremor.
PubMed: 31949348
DOI: 10.4103/ijri.IJRI_412_18 -
Movement Disorders Clinical Practice 2017
PubMed: 30713964
DOI: 10.1002/mdc3.12366 -
Frontiers in Neuroscience 2019Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the...
Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T-weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.
PubMed: 31440122
DOI: 10.3389/fnins.2019.00764 -
The Journal of Neuroscience : the... Nov 2023The medial nucleus of the trapezoid body (MNTB) in the auditory brainstem is the principal source of synaptic inhibition to several functionally distinct auditory...
The medial nucleus of the trapezoid body (MNTB) in the auditory brainstem is the principal source of synaptic inhibition to several functionally distinct auditory nuclei. Prominent projections of individual MNTB neurons comprise the major binaural nuclei that are involved in the early processing stages of sound localization as well as the superior paraolivary nucleus (SPON), which contains monaural neurons that extract rapid changes in sound intensity to detect sound gaps and rhythmic oscillations that commonly occur in animal calls and human speech. While the processes that guide the development and refinement of MNTB axon collaterals to the binaural nuclei have become increasingly understood, little is known about the development of MNTB collaterals to the monaural SPON. In this study, we investigated the development of MNTB-SPON connections in mice of both sexes from shortly after birth to three weeks of age, which encompasses the time before and after hearing onset. Individual axon reconstructions and electrophysiological analysis of MNTB-SPON connectivity demonstrate a dramatic increase in the number of MNTB axonal boutons in the SPON before hearing onset. However, this proliferation was not accompanied by changes in the strength of MNTB-SPON connections or by changes in the structural or functional topographic precision. However, following hearing onset, the spread of single-axon boutons along the tonotopic axis increased, indicating an unexpected decrease in the tonotopic precision of the MNTB-SPON pathway. These results provide new insight into the development and organization of inhibition to SPON neurons and the regulation of developmental plasticity in diverging inhibitory pathways. The superior paraolivary nucleus (SPON) is a prominent auditory brainstem nucleus involved in the early detection of sound gaps and rhythmic oscillations. The ability of SPON neurons to fire at the offset of sound depends on strong and precise synaptic inhibition provided by glycinergic neurons in the medial nucleus of the trapezoid body (MNTB). Here, we investigated the anatomic and physiological maturation of MNTB-LSO connectivity in mice before and after the onset of hearing. We observed a period of bouton proliferation without accompanying changes in topographic precision before hearing onset. This was followed by bouton elimination and an unexpected decrease in the tonotopic precision after hearing onset. These results provide new insight into the development of inhibition to the SPON.
Topics: Male; Female; Mice; Animals; Humans; Auditory Pathways; Olivary Nucleus; Trapezoid Body; Superior Olivary Complex; Neurons
PubMed: 37734946
DOI: 10.1523/JNEUROSCI.0920-23.2023