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Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters.

ABSTRACT: The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.

SUBMITTER: Turecek J

PROVIDER: S-EPMC7707816 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters.

Turecek Josef J Regehr Wade G WG

eLife 20201201

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are tw ...[more]

PMID: 33259288

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Project description:Adaptations of vestibulo-ocular and optokinetic response eye movements have been studied as an experimental model of cerebellum-dependent motor learning. Several previous physiological and pharmacological studies have consistently suggested that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may respectively maintain the memory traces of short- and long-term adaptation. To study the basic structures of the FL-MVN synapses by light microscopy (LM) and electron microscopy (EM), we injected green florescence protein (GFP)-expressing lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice. The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the border region of parvocellular MVN and prepositus hypoglossi (PrH). In the magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal synaptic boutons mainly terminated on the relatively small-diameter (< 1 μm) distal dendrites of MVN neurons, forming symmetrical synapses. The majority of such parvocellular MVN/PrH neurons were determined to be glutamatergic by immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice. To further examine the spatial relationship between the synapses of FL P-cells and those of vestibular nerve on the neurons of the parvocellular MVN/PrH, we added injections of biotinylated dextran amine into the semicircular canal and anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular nerve synaptic boutons in both LM and EM studies. Such a partial overlap of synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells may influence the function of neighboring excitatory synapses of vestibular nerve in the parvocellular MVN/PrH neurons.

Project description:BackgroundThe clinical features and therapeutic measures of vestibular schwannoma (VS) radiation-related aneurysm (RRA) have not been well described. We reported the first VS RRA case admitted for acute anterior inferior cerebella artery (AICA) ischemic symptoms. Literature was reviewed to present the research fruits about VS RRAs, and some therapeutic advices were given.Materials and methodsA 54-year-old woman who had undergone GKS 10 years previously for a right VS was admitted to our hospital in 2018 because of sudden onset of severe vertigo and vomiting, accompanied with unsteady gait. During tumor resection, a dissecting aneurysm arose from the main trunk of AICA was encountered accidently within the tumor. The aneurysm was successfully treated with direct clip ligation, sparing the parent vessel. Data about this case were combined with those of other 11 radiation-related AICA aneurysm cases retrieved from the current literature. The following parameters were evaluated: Age, Sex, Diagnostic method, Location of aneurysm, Age of radiotherapy (Years)/Latency, Rupture, x-ray dosage, Type of radiotherapy, History of surgical resection of VS, Aneurysm Type, Morphology, Number, Treatment, Operative complications, Sequela, Outcome. VS RRAs mainly occurred in women (75%) with a median age of 62.5 years and were mainly located on AICA. Ruptured aneurysms accounted for 75.0% of the total cases. This paper reported the first VS case admitted with acute AICA ischemic symptoms. Cases with sacciform-like, irregular and fusiform-shaped aneurysms accounted for 50.0%, 25.0% and 25.0% of the total, respectively. After surgical treatment, 75.0% patients recovered, except for 3 patients who developed new ischemic consequence.ConclusionPatients should be informed of the risk of RRAs after receiving radiotherapy for VS. In these patients, RRAs should be suspected when subarachnoid hemorrhage or AICA ischemic symptoms occurred. Active intervention should be conducted considering the high instability and bleeding rate of VS RRAs.

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Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters.

Publications

Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters.

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