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ELife Aug 2023The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of...
The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the output of olivary neurons. Here, we use mouse models to investigate how the inhibitory and excitatory inputs to the olivary neurons interact with each other, generating spiking patterns of olivary neurons that align with their intrinsic oscillations. Using dual color optogenetic stimulation and whole-cell recordings, we demonstrate how intervals between the inhibitory input from the cerebellar nuclei and excitatory input from the mesodiencephalic junction affect phase and gain of the olivary output at both the sub- and suprathreshold level. When the excitatory input is activated shortly (~50 ms) after the inhibitory input, the phase of the intrinsic oscillations becomes remarkably unstable and the excitatory input can hardly generate any olivary spike. Instead, when the excitatory input is activated one cycle (~150 ms) after the inhibitory input, the excitatory input can optimally drive olivary spiking, riding on top of the first cycle of the subthreshold oscillations that have been powerfully reset by the preceding inhibitory input. Simulations of a large-scale network model of the inferior olive highlight to what extent the synaptic interactions penetrate in the neuropil, generating quasi-oscillatory spiking patterns in large parts of the olivary subnuclei, the size of which also depends on the relative timing of the inhibitory and excitatory inputs.
Topics: Mice; Animals; Cerebellar Nuclei; Olivary Nucleus; Neurons; Purkinje Cells; Cerebellum; Action Potentials
PubMed: 37526175
DOI: 10.7554/eLife.83239 -
Journal of Otology Apr 2022Objective tinnitus is defined as a type of tinnitus perceived by both the patient and external observer. This paper presents two cases of objective tinnitus related to... (Review)
Review
Objective tinnitus is defined as a type of tinnitus perceived by both the patient and external observer. This paper presents two cases of objective tinnitus related to palatal tremor, along with a literature review. Palatal tremor is a condition characterized by soft palate involuntary contractions. Two types of palatal tremor have been described: symptomatic palatal tremor and essential palatal tremor, with different clinical manifestations. Diagnostic workup is based on medical history and physical examination, including direct oropharynx exploration and cavum visualization through nasopharyngoscopy. Brain MRI is mandatory in all cases. If a secondary origin is suspected, additional lab tests should be performed based on clinical suspicion. First-line treatment is botulinum toxin injection into the and muscles, with velopharyngeal insufficiency being its main adverse effect. Other medications have not been shown to be effective.
PubMed: 35949555
DOI: 10.1016/j.joto.2021.11.003 -
Frontiers in Neural Circuits 2022The lateral superior olive (LSO) is a key structure in the central auditory system of mammals that exerts efferent control on cochlear sensitivity and is involved in the...
The lateral superior olive (LSO) is a key structure in the central auditory system of mammals that exerts efferent control on cochlear sensitivity and is involved in the processing of binaural level differences for sound localization. Understanding how the LSO contributes to these processes requires knowledge about the resident cells and their connections with other auditory structures. We used standard histological stains and retrograde tracer injections into the inferior colliculus (IC) and cochlea in order to characterize two basic groups of neurons: (1) Principal and periolivary (PO) neurons have projections to the IC as part of the ascending auditory pathway; and (2) lateral olivocochlear (LOC) intrinsic and shell efferents have descending projections to the cochlea. Principal and intrinsic neurons are intermixed within the LSO, exhibit fusiform somata, and have disk-shaped dendritic arborizations. The principal neurons have bilateral, symmetric, and tonotopic projections to the IC. The intrinsic efferents have strictly ipsilateral projections, known to be tonotopic from previous publications. PO and shell neurons represent much smaller populations (<10% of principal and intrinsic neurons, respectively), have multipolar somata, reside outside the LSO, and have non-topographic, bilateral projections. PO and shell neurons appear to have widespread projections to their targets that imply a more diffuse modulatory function. The somata and dendrites of principal and intrinsic neurons form a laminar matrix within the LSO and share quantifiably similar alignment to the tonotopic axis. Their restricted projections emphasize the importance of frequency in binaural processing and efferent control for auditory perception. This study addressed and expanded on previous findings of cell types, circuit laterality, and projection tonotopy in the LSO of the mouse.
Topics: Animals; Mice; Superior Olivary Complex; Olivary Nucleus; Auditory Pathways; Inferior Colliculi; Neurons; Mammals
PubMed: 36338332
DOI: 10.3389/fncir.2022.1038500 -
Neuroscience Research Sep 2021The principal olivary nucleus is the largest part of the inferior olivary complex and is involved in the spatial and temporal organization of movement and motor...
The principal olivary nucleus is the largest part of the inferior olivary complex and is involved in the spatial and temporal organization of movement and motor learning. Nearly all neurons in this nucleus is multipolar along with having a highly complex dendritic tree and significant asymmetry in shape. In this study, we updated the current classification scheme, examined morphological differences between the proposed groups, and investigated age-related morphological changes. Histological preparations were digitized by a light microscope and a sample of 259 images of neurons was analyzed by 17 computationally generated parameters of morphology. These were reduced to the four variables of principal component analysis and the sample was classified by k-means method of clustering into three clusters. The differences between clusters were documented and for medium-sized neurons the relationship between four morphological parameters and age were investigated. Finally, for two of the age groups the changes in the morphology were explored. This study includes a detailed and robust classification of the PON neurons and the findings improve upon past qualitative work.
Topics: Humans; Neurons; Olivary Nucleus
PubMed: 33347909
DOI: 10.1016/j.neures.2020.10.005 -
Journal of Child Neurology Feb 2022To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response.
AIM
To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response.
METHODS
Prospective study was done including 12 patients with Crigler Najjar syndrome type I and 10 age- and sex-matched controls that underwent diffusion tensor imaging of brain. Mean diffusivity and fractional anisotropy at 4 regions of the brain and brainstem on each side were measured and correlated with the results of auditory brainstem response for patients.
RESULTS
There was significantly higher mean diffusivity of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls on both sides for all regions ( = .001). The fractional anisotropy of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls was significantly lower, with values of, respectively, .001, .001, .003, and .001 on the right side and .001, .001, .003, and .001 on left side, respectively. Also, a negative correlation was found between the maximum bilirubin level and fractional anisotropy of the left superior olivary nucleus and inferior colliculus of both sides. A positive correlation was found between the mean diffusivity and auditory brainstem response wave latency of the right inferior colliculus and left cochlear nucleus. The fractional anisotropy and auditory brainstem response wave latency of the right superior olivary nucleus, left cochlear nucleus, and inferior colliculus of both sides were negatively correlated.
CONCLUSION
Diffusion tensor imaging can detect microstructural changes in the auditory pathway in Crigler Najjar syndrome type I that can be correlated with auditory brainstem response.
Topics: Adult; Auditory Pathways; Crigler-Najjar Syndrome; Diffusion Tensor Imaging; Evoked Potentials, Auditory, Brain Stem; Female; Humans; Male; Middle Aged; Prospective Studies
PubMed: 34961382
DOI: 10.1177/08830738211025865 -
Frontiers in Neurology 2021The abnormal T1-weighted imaging of MRI can be used to characterize neonatal acute bilirubin encephalopathy (ABE) in newborns, but has limited use in evaluating the...
The abnormal T1-weighted imaging of MRI can be used to characterize neonatal acute bilirubin encephalopathy (ABE) in newborns, but has limited use in evaluating the severity and prognosis of ABE. This study aims to assess the value of diffusion kurtosis imaging (DKI) in detecting ABE and understanding its pathogenesis. Seventy-six newborns with hyperbilirubinemia were grouped into three groups (mild group, moderate group, and severe group) based on serum bilirubin levels. All the patients underwent conventional MRI and DKI serial, as well as 40 healthy full-term infants (control group). The regions of interest (ROIs) were the bilateral globus pallidus, dorsal thalamus, frontal lobe, auditory radiation, superior temporal gyrus, substantia nigra, hippocampus, putamen, and inferior olivary nucleus. The values of mean diffusivity (MD), axial kurtosis (AK), radial kurtosis (RK), and mean kurtosis (MK), and fractional anisotropy (FA), radial diffusivity (RD), and axis diffusivity (AD) of the ROIs were evaluated. All newborns were followed up and evaluated using the Denver Development Screening Test (DDST). According to the follow-up results, the patients were divided into the normal group, the suspicious abnormal group, and the abnormal group. Compared with the control group, significant differences were observed with the increased MK of dorsal thalamus, AD of globus pallidus in the moderate group, and increased RD, MK, AK, and RK value of globus pallidus, dorsal thalamus, auditory radiation, superior temporal gyrus, and hippocampus in the severe group. The peak value of total serum bilirubin was moderately correlated with the MK of globus pallidus, dorsal thalamus, and auditory radiation and was positively correlated with the other kurtosis value. Out of 76 patients, 40 finished the DDST, and only 9 patients showed an abnormality. Compared with the normal group, the AK value of inferior olivary nucleus showed significant differences ( < 0.05) in the suspicious abnormal group, and the MK of globus pallidus, temporal gyrus, and auditory radiation; RK of globus pallidus, dorsal thalamus, and auditory radiation; and MD of globus pallidus showed significant differences ( < 0.05) in the abnormal group. DKI can reflect the subtle structural changes of neonatal ABE, and MK is a sensitive indicator to indicate the severity of brain damage.
PubMed: 34512498
DOI: 10.3389/fneur.2021.645534 -
The Journal of Neuroscience : the... Jan 2022Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how...
Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways are wired. Defining the anatomy of secondary neurons in the spinal cord that integrate and relay proprioceptive and potentially cutaneous information from the periphery to the cerebellum is fundamental to understanding how proprioceptive circuits function. Here, we define the unique anatomic trajectories of long-range direct and indirect spinocerebellar pathways as well as local intersegmental spinal circuits using genetic tools in both male and female mice. We find that Clarke's column neurons, a major contributor to the direct spinocerebellar pathway, has mossy fiber terminals that diversify extensively in the cerebellar cortex with axons terminating bilaterally, but with no significant axon collaterals within the spinal cord, medulla, or cerebellar nuclei. By contrast, we find that two of the indirect pathways, the spino-lateral reticular nucleus and spino-olivary pathways, are in part, derived from cervical -lineage neurons, whereas thoracolumbar -lineage neurons project mostly locally within the spinal cord. Notably, while cervical and thoracolumbar -lineage neurons connect locally with motor neurons, no Clarke's column to motor neuron connections were detected. Together, we define anatomic differences between long-range direct, indirect, and local proprioceptive subcircuits that likely mediate different components of proprioceptive-motor behaviors. We define the anatomy of long-range direct and indirect spinocerebellar pathways as well as local spinal proprioceptive circuits. We observe that mossy fiber axon terminals of Clarke's column neurons diversify proprioceptive information across granule cells in multiple lobules on both ipsilateral and contralateral sides, sending no significant collaterals within the spinal cord, medulla, or cerebellar nuclei. Strikingly, we find that cervical spinal cord -lineage neurons form mainly the indirect spino-lateral reticular nucleus and spino-olivary tracts and thoracolumbar -lineage neurons project locally within the spinal cord, whereas only a few -lineage neurons form a direct spinocerebellar tract.
Topics: Animals; Animals, Newborn; Cerebellum; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Proprioception; Spinal Cord; Spinocerebellar Tracts
PubMed: 34857649
DOI: 10.1523/JNEUROSCI.2157-20.2021 -
Hearing Research Dec 2019Bushy cells of the ventral cochlear nucleus are time-coding neurons. They receive axosomatic synaptic terminals from the auditory nerve, the so-called endbulb of Held... (Review)
Review
Bushy cells of the ventral cochlear nucleus are time-coding neurons. They receive axosomatic synaptic terminals from the auditory nerve, the so-called endbulb of Held synapses and project to sound localization centers in the superior olivary complex. Bushy cells are specialized to maintain and even improve the temporal code contained in the auditory nerve activity. In the present review an overview is given of the dynamic features and convergent inputs that modulate the response of bushy cells to auditory stimuli. The biophysics and synaptic specializations and dynamics of these neurons were studied extensively. These studies will be reviewed briefly in the initial part of this paper. In addition to auditory nerve input, powerful but slow inhibitory inputs act on bushy cells. Studies on these inhibitory inputs to bushy cells are discussed as part of this review. Furthermore, evidence for four classes of additional or secondary inputs that also impinge on the bushy cells will be reviewed: 1) small auditory nerve boutons, 2) commissural connections that are either inhibitory or excitatory, 3) multimodal inputs from somatosensory nuclei and 4) descending modulatory axons employing monoaminergic transmitters all interact with the main auditory nerve input in the bushy cells. The present article aims at reviewing how complex the influences on neuronal processing are, already in this early stage of the auditory pathway. It is concluded that the various modulatory influences help to better adapt bushy cell coding functions to dynamics of the sensory world.
Topics: Acoustic Stimulation; Animals; Auditory Pathways; Cochlear Nucleus; Humans; Neural Inhibition; Neurons; Periodicity; Sound Localization; Synaptic Transmission; Time Perception
PubMed: 31670183
DOI: 10.1016/j.heares.2019.107824 -
The Journal of Neuroscience : the... Apr 2023Comparative analysis of evolutionarily conserved neuronal circuits between phylogenetically distant mammals highlights the relevant mechanisms and specific adaptations...
Comparative analysis of evolutionarily conserved neuronal circuits between phylogenetically distant mammals highlights the relevant mechanisms and specific adaptations to information processing. The medial nucleus of the trapezoid body (MNTB) is a conserved mammalian auditory brainstem nucleus relevant for temporal processing. While MNTB neurons have been extensively investigated, a comparative analysis of phylogenetically distant mammals and the spike generation is missing. To understand the suprathreshold precision and firing rate, we examined the membrane, voltage-gated ion channel and synaptic properties in (bat) and in (rodent) of either sex. Between the two species, the membrane properties of MNTB neurons were similar at rest with only minor differences, while larger dendrotoxin (DTX)-sensitive potassium currents were found in gerbils. Calyx of Held-mediated EPSCs were smaller and frequency dependence of short-term plasticity (STP) less pronounced in bats. Simulating synaptic train stimulations in dynamic clamp revealed that MNTB neurons fired with decreasing success rate near conductance threshold and at increasing stimulation frequency. Driven by STP-dependent conductance decrease, the latency of evoked action potentials increased during train stimulations. The spike generator showed a temporal adaptation at the beginning of train stimulations that can be explained by sodium current inactivation. Compared with gerbils, the spike generator of bats sustained higher frequency input-output functions and upheld the same temporal precision. Our data mechanistically support that MNTB input-output functions in bats are suited to sustain precise high-frequency rates, while for gerbils, temporal precision appears more relevant and an adaptation to high output-rates can be spared. Neurons in the mammalian medial nucleus of the trapezoid body (MNTB) convey precise, faithful inhibition vital for binaural hearing and gap detection. The MNTB's structure and function appear evolutionarily well conserved. We compared the cellular physiology of MNTB neurons in bat and gerbil. Because of their adaptations to echolocation or low frequency hearing both species are model systems for hearing research, yet with largely overlapping hearing ranges. We find that bat neurons sustain information transfer with higher ongoing rates and precision based on synaptic and biophysical differences in comparison to gerbils. Thus, even in evolutionarily conserved circuits species-specific adaptations prevail, highlighting the importance for comparative research to differentiate general circuit functions and their specific adaptations.
Topics: Animals; Action Potentials; Trapezoid Body; Chiroptera; Gerbillinae; Neurons; Auditory Pathways
PubMed: 36898837
DOI: 10.1523/JNEUROSCI.2320-22.2023 -
Frontiers in Neural Circuits 2024The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The... (Comparative Study)
Comparative Study
The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.
Topics: Animals; Rats; Mice; Male; Neural Pathways; Intralaminar Thalamic Nuclei; Mice, Inbred C57BL; Rats, Sprague-Dawley; Female
PubMed: 38736977
DOI: 10.3389/fncir.2024.1384621