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ENeuro Feb 2024The olivocerebellar system, which is critical for sensorimotor performance and learning, functions through modules with feedback loops. The main feedback to the inferior...
The olivocerebellar system, which is critical for sensorimotor performance and learning, functions through modules with feedback loops. The main feedback to the inferior olive comes from the cerebellar nuclei (CN), which are predominantly GABAergic and contralateral. However, for the subnucleus d of the caudomedial accessory olive (cdMAO), a crucial region for oculomotor and upper body movements, the source of GABAergic input has yet to be identified. Here, we demonstrate the existence of a disynaptic inhibitory projection from the medial CN (MCN) to the cdMAO via the superior colliculus (SC) by exploiting retrograde, anterograde, and transsynaptic viral tracing at the light microscopic level as well as anterograde classical and viral tracing combined with immunocytochemistry at the electron microscopic level. Retrograde tracing in Gad2-Cre mice reveals that the cdMAO receives GABAergic input from the contralateral SC. Anterograde transsynaptic tracing uncovered that the SC neurons receiving input from the contralateral MCN provide predominantly inhibitory projections to contralateral cdMAO, ipsilateral to the MCN. Following ultrastructural analysis of the monosynaptic projection about half of the SC terminals within the contralateral cdMAO are GABAergic. The disynaptic GABAergic projection from the MCN to the ipsilateral cdMAO mirrors that of the monosynaptic excitatory projection from the MCN to the contralateral cdMAO. Thus, while completing the map of inhibitory inputs to the olivary subnuclei, we established that the MCN inhibits the cdMAO via the contralateral SC, highlighting a potential push-pull mechanism in directional gaze control that appears unique in terms of laterality and polarity among olivocerebellar modules.
Topics: Mice; Animals; Inferior Olivary Complex; Cerebellum; Olivary Nucleus; Synaptic Transmission; Cerebellar Nuclei
PubMed: 38242692
DOI: 10.1523/ENEURO.0262-23.2023 -
The Journal of Neuroscience : the... Feb 2024The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. Here, we investigate sensory representations in the inferior olive (IO) of larval...
The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. Here, we investigate sensory representations in the inferior olive (IO) of larval zebrafish and their spatial organization. Using single-cell labeling of genetically identified IO neurons, we find that they can be divided into at least two distinct groups based on their spatial location, dendritic morphology, and axonal projection patterns. In the same genetically targeted population, we recorded calcium activity in response to a set of visual stimuli using two-photon imaging. We found that most IO neurons showed direction-selective and binocular responses to visual stimuli and that the functional properties were spatially organized within the IO. Light-sheet functional imaging that allowed for simultaneous activity recordings at the soma and axonal level revealed tight coupling between functional properties, soma location, and axonal projection patterns of IO neurons. Taken together, our results suggest that anatomically defined classes of IO neurons correspond to distinct functional types, and that topographic connections between IO and cerebellum contribute to organization of the cerebellum into distinct functional zones.
Topics: Animals; Zebrafish; Larva; Olivary Nucleus; Neurons; Cerebellum
PubMed: 38195508
DOI: 10.1523/JNEUROSCI.2352-21.2023 -
Bio Systems Feb 2024In this paper, based on the four variables Kazantsev et al. inferior olive neuron (ION) dynamic equations, a five variables neuron model is designed to describe the... (Review)
Review
In this paper, based on the four variables Kazantsev et al. inferior olive neuron (ION) dynamic equations, a five variables neuron model is designed to describe the effect of electromagnetic induction in ION activities. Within the new ION model, the effect of magnetic flow on membrane potential is described by imposing additive memristive current in the master block of the Kasantsev et al. neuron model. The impact of magnetic flux on the stability of equilibrium point is studied. Hopf bifurcation and bifurcation diagram indicated that, as the electromagnetic field strength parameter changes, the value of the critical point also changes. Furthermore, as the electromagnetic induction is increasing, there is appearance of bursting dynamic in the slave subsystem and an increase in the spike amplitude of the master subsystem. In addition, the analog circuit of the master block confirms the observed results from numerical simulation.
Topics: Models, Neurological; Neurons; Membrane Potentials; Electromagnetic Fields; Inferior Olivary Complex
PubMed: 38176519
DOI: 10.1016/j.biosystems.2023.105114 -
Glia Apr 2024Axons of globular bushy cells in the cochlear nucleus convey hyper-accurate signals to the superior olivary complex, the initial site of binaural processing via...
Axons of globular bushy cells in the cochlear nucleus convey hyper-accurate signals to the superior olivary complex, the initial site of binaural processing via comparably thick axons and the calyx of the Held synapse. Bushy cell fibers involved in hyper-accurate binaural processing of low-frequency sounds are known to have an unusual internode length-to-axon caliber ratio (L/d) correlating with higher conduction velocity and superior temporal precision of action potentials. How the L/d-ratio develops and what determines this unusual myelination pattern is unclear. Here we describe a gradual developmental transition from very simple to complex, mature nodes of Ranvier on globular bushy cell axons during a 2-week period starting at postnatal day P6/7. The molecular composition of nodes matured successively along the axons from somata to synaptic terminals with morphologically and molecularly mature nodes appearing almost exclusively after hearing onset. Internodal distances are initially coherent with the canonical L/d-ratio of ~100. Several days after hearing onset, however, an over-proportional increase in axon caliber occurs in cells signaling low-frequency sounds which alters their L/d ratio to ~60. Hence, oligodendrocytes initially myelinating axons according to their transient axon caliber but a subsequent differential axon thickening after hearing onset results in the unusual myelination pattern.
Topics: Action Potentials; Axons; Neurons; Presynaptic Terminals; Oligodendroglia; Myelin Sheath
PubMed: 38174817
DOI: 10.1002/glia.24504 -
Frontiers in Neural Circuits 2023Auditory brainstem neurons in the lateral superior olive (LSO) receive excitatory input from the ipsilateral cochlear nucleus (CN) and inhibitory transmission from the...
Auditory brainstem neurons in the lateral superior olive (LSO) receive excitatory input from the ipsilateral cochlear nucleus (CN) and inhibitory transmission from the contralateral CN via the medial nucleus of the trapezoid body (MNTB). This circuit enables sound localization using interaural level differences. Early studies have observed an additional inhibitory input originating from the ipsilateral side. However, many of its details, such as its origin, remained elusive. Employing electrical and optical stimulation of afferents in acute mouse brainstem slices and anatomical tracing, we here describe a glycinergic projection to LSO principal neurons that originates from the ipsilateral CN. This inhibitory synaptic input likely mediates inhibitory sidebands of LSO neurons in response to acoustic stimulation.
Topics: Animals; Mice; Superior Olivary Complex; Cochlear Nucleus; Olivary Nucleus; Sound Localization; Neurons; Auditory Pathways
PubMed: 38107610
DOI: 10.3389/fncir.2023.1307283 -
Journal of the Association For Research... Dec 2023The role of the medial olivocochlear system in speech perception in noise has been debated over the years, with studies showing mixed results. One possible reason for...
PURPOSE
The role of the medial olivocochlear system in speech perception in noise has been debated over the years, with studies showing mixed results. One possible reason for this could be the dependence of this relationship on the parameters used in assessing the speech perception ability (age, stimulus, and response-related variables).
METHODS
The current study assessed the influence of the type of speech stimuli (monosyllables, words, and sentences), the signal-to-noise ratio (+5, 0, -5, and -10 dB), the metric used to quantify the speech perception ability (percent-correct, SNR-50, and slope of the psychometric function) and age (young vs old) on the relationship between medial olivocochlear reflex (quantified by contralateral inhibition of transient evoked otoacoustic emissions) and speech perception in noise.
RESULTS
A linear mixed-effects model revealed no significant contributions of the medial olivocochlear reflex to speech perception in noise.
CONCLUSION
The results suggest that there was no evidence of any modulatory influence of the indirectly measured medial olivocochlear reflex strength on speech perception in noise.
Topics: Speech Perception; Otoacoustic Emissions, Spontaneous; Speech; Noise; Reflex; Cochlea; Olivary Nucleus; Acoustic Stimulation
PubMed: 38079021
DOI: 10.1007/s10162-023-00919-w -
Clinical Neurophysiology : Official... Jan 2024
Topics: Humans; Myoclonus; Olivary Degeneration; Cerebral Hemorrhage; Stereotaxic Techniques; Brain; Olivary Nucleus; Hypertrophy; Magnetic Resonance Imaging
PubMed: 38052148
DOI: 10.1016/j.clinph.2023.11.009 -
The Journal of the Acoustical Society... Dec 2023An auditory model has been developed with a time-varying, gain-control signal based on the physiology of the efferent system and subcortical neural pathways. The medial...
An auditory model has been developed with a time-varying, gain-control signal based on the physiology of the efferent system and subcortical neural pathways. The medial olivocochlear (MOC) efferent stage of the model receives excitatory projections from fluctuation-sensitive model neurons of the inferior colliculus (IC) and wide-dynamic-range model neurons of the cochlear nucleus. The response of the model MOC stage dynamically controls cochlear gain via simulated outer hair cells. In response to amplitude-modulated (AM) noise, firing rates of most IC neurons with band-enhanced modulation transfer functions in awake rabbits increase over a time course consistent with the dynamics of the MOC efferent feedback. These changes in the rates of IC neurons in awake rabbits were employed to adjust the parameters of the efferent stage of the proposed model. Responses of the proposed model to AM noise were able to simulate the increasing IC rate over time, whereas the model without the efferent system did not show this trend. The proposed model with efferent gain control provides a powerful tool for testing hypotheses, shedding insight on mechanisms in hearing, specifically those involving the efferent system.
Topics: Animals; Rabbits; Inferior Colliculi; Cochlear Nucleus; Efferent Pathways; Cochlea; Hearing; Olivary Nucleus; Auditory Pathways
PubMed: 38051523
DOI: 10.1121/10.0022578 -
Journal of Neurology, Neurosurgery, and... May 2024
Topics: Humans; alpha-Synuclein; Olivary Nucleus; Multiple System Atrophy; Cerebellum; Male; Autopsy; Functional Laterality; Aged; Middle Aged; Female
PubMed: 37989568
DOI: 10.1136/jnnp-2023-332419 -
Brain Pathology (Zurich, Switzerland) May 2024Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia,...
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA. We examined 97 spinal cords from consecutively autopsied patients with MSA. Myelin staining revealed that 22 cords (22.7%) had small, bilateral, triangular-shaped tract degeneration in the boundary of the anterior and lateral funiculi, which appeared continuously from C1 to C5. The anatomical pathway of the degenerated tract was consistent with the description of the olivospinal tract provided by Helweg in 1888. The MSA patients showing degeneration of this tract were younger at disease onset (average: 56.4 ± 8.7 years, range: 42-74), and had longer disease duration (average: 10.1 ± 4.8 years, range: 2-25) and more severe olivopontocerebellar changes compared to other MSA patients. Quantitative analyses revealed that patients with olivospinal tract degeneration had a lower neuronal density in the inferior olivary nucleus compared to other patients. Microglial density in this tract was negatively correlated with the neuronal density in the inferior olivary nucleus. The densities of glial cytoplasmic inclusions in the inferior olivary nucleus and in the olivospinal tract were strongly correlated with each other. Neurologically healthy controls (n = 22) and disease controls with Lewy body disease (n = 30), amyotrophic lateral sclerosis (n = 30), and progressive supranuclear palsy (n = 30) did not present the olivospinal tract degeneration. Our results indicate an impairment of the neural connection between the inferior olivary nucleus and the spinal cord in MSA patients, which may develop in a descending manner.
Topics: Adult; Humans; Multiple System Atrophy; alpha-Synuclein; Cervical Cord; Olivopontocerebellar Atrophies
PubMed: 37972988
DOI: 10.1111/bpa.13226