Subnuclei Of Inferior Olive Research Articles

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

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.

The transgenic mouse line Igsf9-eGFP allows targeted stimulation of inferior olive efferents

BackgroundThe inferior olive (IO) innervates the cerebellum forming synapses in the deep cerebellar nuclei (DCN) and the cerebellar cortex. Beside the well-known exception of synapses on Purkinje neurons, synapses between IO efferents and other neuronal targets have not been studied intensively, mostly due to the technical challenge of unequivocally identifying IO efferents in electrophysiological experiments. New methodWe describe the transgenic mouse line Igsf9-eGFP, which expresses GFP in IO neurons, as a suitable tool for studying IO efferents using live imaging, immunohistochemistry and electrophysiology. ResultsIn the Igsf9-eGFP line, GFP-positive neurons are found in all IO subnuclei. Their efferents show the expected trajectories innervating the DCN and, as climbing fibers (CFs), the cerebellar cortex. In the DCN the dentate nucleus shows the strongest innervation, and, within the cerebellar cortex, CFs show a rostral-to-caudal gradient. GFP-positive CFs undergo a normal postnatal maturation, and evoke normal synaptic responses in Purkinje neurons and DCN neurons. Comparison with existing methodsIO efferents have been labelled via anterograde labelling, viral transfection and in transgenic mouse lines. The latter approach does not require stereotactic injections. However, available mouse lines show only a sparse GFP expression, harbor GFP-positive axons of other cerebellar fibers, or have not been characterized in detail. ConclusionsThe Igsf9-eGFP line is characterized by a moderate density of GFP-positive IO efferents, which can be visually targeted for extracellular stimulation with micrometer precision. The mouse line will allow studying fiber-specific responses in all neurons targeted by the IO.

Extracellular matrix molecules exhibit unique expression pattern in the climbing fiber-generating precerebellar nucleus, the inferior olive

Extracellular matrix (ECM) accumulates around different neuronal compartments of the central nervous system (CNS) or appears in diffuse reticular form throughout the neuropil. In the adult CNS, the perineuronal net (PNN) surrounds the perikarya and dendrites of various neuron types, whereas the axonal coats are aggregations of ECM around the individual synapses, and the nodal ECM is localized at the nodes of Ranvier. Previous studies in our laboratory demonstrated on rats that the heterogeneous distribution and molecular composition of ECM is associated with the variable cytoarchitecture and hodological organization of the vestibular nuclei and may also be related to their specific functions in gaze and posture control as well as in the compensatory mechanisms following vestibular lesion. Here, we investigated the ECM expression pattern in the climbing fiber-generating inferior olive (IO), which is functionally related to the vestibular nuclei. By using histochemical and immunohistochemical methods, the most characteristic finding was the lack of PNNs, presumably due to the absence of synapses on the perikarya and proximal dendrites of IO neurons. On the other hand, the darkly stained dots or ring-like structures in the neuropil might represent the periaxonal coats around the axon terminals of olivary synaptic glomeruli. We have observed positive ECM reaction for the hyaluronan, tenascin-R, hyaluronan and proteoglycan link protein 1 (HAPLN1) and various chondroitin sulfate proteoglycans. The staining intensity and distribution of ECM molecules revealed a number of differences between the functionally different subnuclei of IO. We hypothesized that the different molecular composition and intensity differences of ECM reaction is associated with different control mechanisms of gaze and posture control executed by the visuomotor-vestibular, somatosensory and integrative subnuclei of the IO.

Topography of Inferior Olivary Neurons that Encode Canal and Otolith Inputs

Vestibular information arising from rotational head movement and that from translational head movement are detected respectively by the semicircular canal and otolith organ in the inner ear. Spatiotemporal cues are in turn processed by the vestibulo-olivo-cerebellar pathway for sensorimotor coordination, but the role of the inferior olive (IO) in this pathway remains unclear. To address whether rotational and translational movements are differentially represented in the IO, we studied the distribution pattern of IO neurons recruited into the circuitry following selective activation of receptor hair cells of the horizontal semicircular canal or the utricle in adult rats. Neurons in the beta nucleus of IO (IOβ) and dorso-medial cell column of IO were responsive to horizontal translation, but not rotation. Notably, otolith-related neurons were observable largely in the rostral IOβ. In contrast, the subnucleus A of IO (IOA), subnucleus C of IO (IOC), and dorsal cap of Kooy (IOK) were responsive to horizontal rotation, but not translation. In the IOA, these canal-related neurons were clustered in the medial portion of the subnucleus. In the IOC, canal-related neurons were skewed towards the rostral half. In the IOK, canal-related neurons were found throughout the subnucleus. These indicate that the distributions of canal- and otolith-related neurons encoding horizontal motions are clearly segregated in the IO. These discrete IO subnuclei therefore provide a topographic map for temporal and adaptive operations of sensorimotor coordination and spatial reference.

The pattern of c-Fos immunoreactivity in the hindbrain of the rat following stomach distension.

It has been previously shown that the walls of the stomach contain vagal and splanchnic afferents, connected to low and high threshold (LT and HT) gastric receptors, that convey physiological and noxious information to areas of the hindbrain involved mainly in the control of gastrointestinal function. Because distension of the stomach also reflexly increases the sympathetic drive to the cardiovascular system, the present study was planned to examine the pattern of activation of all nuclei encountered throughout the hindbrain in response to gastric distension. In anaesthetized rats, the stimulus was controlled by employing different transmural pressures and frequencies of distension, and c-Fos immunohistochemistry was used to characterize neuronal activation. Low intensity stimulation induced c-Fos expression in the cranial part of nucleus of solitary tract (NTS), the nucleus ambiguus (NA), the lateral reticular area (LRt) and the ventrolateral medulla (RVL/CVL). At low frequency of stimulation c-Fos positive nuclei (p.n.) were found in NTS only. At high frequency of stimulation an increase in c-Fos immunoreactivity was found. High intensity stimulation induced c-Fos expression in area postrema (AP), the lateral vestibular nucleus (LVe) and the caudal part of the NTS. At low frequency, only the number of c-Fos p.n. was increased. Increasing the frequency of stimulation induced c-Fos expression in further nuclei such as the parabrachial nucleus (PBN), the inferior olive subnuclei (IOn), the oral part of spinal trigeminal nucleus (Sp5O) and locus coeruleus (LC). At higher frequencies c-Fos immunoreactivity decreased in NTS and LRt, disappeared in VLM and increased in NA. Thus stomach distension activated several neuronal excitatory and inhibitory circuits that are involved in the control of gastrointestinal function as well as in cardiovascular, respiratory and pain regulation. The differences in c-Fos immunoreactivity induced by changing the distension patterns suggested interactions between groups of vagal and splanchnic afferents.