scholarly journals Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Antoine M Valera ◽  
Francesca Binda ◽  
Sophie A Pawlowski ◽  
Jean-Luc Dupont ◽  
Jean-François Casella ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Granule Cell ◽  
Motor Coordination ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
Synaptic Organization ◽  
Cerebellar Modules ◽  
Activity Dependent

Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex.

scholarly journals Deficits in Motor Coordination with Aberrant Cerebellar Development in Mice Lacking Testicular Orphan Nuclear Receptor 4

2005 ◽  
Vol 25 (7) ◽  
pp. 2722-2732 ◽  
Author(s):  
Yei-Tsung Chen ◽  
Loretta L. Collins ◽  
Hideo Uno ◽  
Chawnshang Chang
Keyword(s):  
Nuclear Receptor ◽  
Granule Cell ◽  
Motor Coordination ◽  
Granule Cells ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
Abnormal Development ◽  
Cerebellar Development ◽  
Morphological Development ◽  
Orphan Nuclear Receptor

ABSTRACT Since testicular orphan nuclear receptor 4 (TR4) was cloned, its physiological function has remained largely unknown. Throughout postnatal development, TR4-knockout (TR4−/−) mice exhibited behavioral deficits in motor coordination, suggesting impaired cerebellar function. Histological examination of the postnatal TR4−/− cerebellum revealed gross abnormalities in foliation; specifically, lobule VII in the anterior vermis was missing. Further analyses demonstrated that the laminations of the TR4−/− cerebellar cortex were changed, including reductions in the thickness of the molecular layer and the internal granule layer, as well as delayed disappearance of the external granule cell layer (EGL). These lamination irregularities may result from interference with granule cell proliferation within the EGL, delayed inward migration of postmitotic granule cells, and a higher incidence of apoptotis. In addition, abnormal development of Purkinje cells was observed in the postnatal TR4−/− cerebellum, as evidenced by aberrant dendritic arborization and reduced calbindin staining intensity. Expression of Pax-6, Sonic Hedgehog (Shh), astrotactin (Astn), reelin, and Cdk-5, genes correlated with the morphological development of the cerebellum, is reduced in the developing TR4−/− cerebellum. Together, our findings suggest that TR4 is required for normal cerebellar development.

scholarly journals Deposition and role of thrombospondin in the histogenesis of the cerebellar cortex.

1990 ◽  
Vol 110 (4) ◽  
pp. 1275-1283 ◽  
Author(s):  
K S O'Shea ◽  
J S Rheinheimer ◽  
V M Dixit
Keyword(s):  
Cell Migration ◽  
Cerebellar Cortex ◽  
Granule Cell ◽  
Granule Cells ◽  
Cell Layer ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
External Granule Cell Layer ◽  
Dependent Inhibition ◽  
Cell Layers

The patterns of deposition of thrombospondin (TSP), a trimeric extracellular matrix glycoprotein, were determined during the initial establishment of the external granule cell layer and the subsequent inward migration of granule cells forming the molecular and (internal) granule cell layers. The early homogeneous deposition of TSP became restricted to the rhombic lip in the region of granule cell exit from the neuroepithelium, and was present between migrating granule cells. During the later inward migration of granule cells, little TSP was associated with dividing granule cells; it was enriched in premigratory granule cells. With the cessation of migration, TSP was lost except in association with fasciculating axons in the molecular layer where staining persisted briefly. At the EM level, TSP was associated with the leading process of granule cells as they associated with Bergmann glial cells and migrated through the molecular layer. TSP was present within granule cell axons; Purkinje cells and their dendrites, as well as Bergmann glial fibers and endfeet were negative for TSP. When anti-TSP antibodies were added to explant cultures of cerebellar cortex during active granule cell migration, a dose-dependent inhibition of migration was observed. In control cultures, granule cells migrated into the (internal) granule cell layer, while granule cells exposed to anti-TSP antibodies were arrested within the external granule cell layer. These results suggest that TSP plays an important role in the histogenesis of the cerebellar cortex by influencing granule cell migration.

Fiber Connections of the Caudal Corpus Cerebelli, with Special Reference to the Intrinsic Circuitry, in a Teleost (Oreochromis niloticus)

2017 ◽  
Vol 89 (1) ◽  
pp. 15-32 ◽  
Author(s):  
Kosuke Imura ◽  
Naoyuki Yamamoto ◽  
Masami Yoshimoto ◽  
Masato Endo ◽  
Kengo Funakoshi ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Granule Cell ◽  
Cell Layer ◽  
Molecular Layer ◽  
Granule Cell Layer ◽  
Projection Neurons ◽  
Descending Pathways ◽  
Zebrin Ii ◽  
Single Axon ◽  
Efferent Neurons

The caudal part of the corpus cerebelli of Nile tilapia can be divided into dorsal and ventral regions. The granule cell layer of the dorsal (dGL) and ventral (vGL) regions of the caudal corpus cerebelli is known to receive indirect inputs from the telencephalon relayed by the nucleus paracommissuralis. The descending pathways are topographically organized, and the dGL and vGL receive inputs from different dorsal telencephalic parts. The caudal corpus cerebelli, in turn, projects extracerebellar efferents. However, it remains unknown how the descending telencephalic inputs are processed within the cerebellum. Therefore, the present study investigated intrinsic connections of the caudal corpus cerebelli by injecting neural tracers into the molecular layer of dorsal and ventral regions. Injections of tracers into the ventral molecular layer resulted in labeled cells in the vGL and the ganglionic layer of the ventral corpus. The axonal trajectories from labeled cells in the ganglionic layer were analyzed in detail via single-axon reconstructions, which suggested that the terminal portions were confined to the ganglionic layer of the dorsal corpus. No labeled terminals were observed outside the caudal corpus cerebelli. Tracer applications to the dorsal molecular layer resulted in labeled cells not only in the ganglionic layer and the granule cell layer of the dorsal corpus but also in the ganglionic layer of the ventral corpus. The latter finding confirms the presence of intrinsic projections from the ventral region to the dorsal region in the caudal corpus cerebelli. We further revealed that the intrinsic projection neurons are Purkinje cells by immunohistochemistry for zebrin II (aldolase C), which is a marker of Purkinje cells, combined with tracer injections into the dorsal corpus. Unlike injections into the ventral corpus, injections into the dorsal corpus resulted in labeled terminals in extracerebellar structures, such as the nucleus of the medial longitudinal fascicle and reticular formation. The present study suggests that indirect inputs from different telencephalic parts received and processed by distinct regions of caudal corpus cerebelli are sent out of the corpus through the efferent neurons in the dorsal corpus.

In Vivo Intracellular Analysis of Granule Cell Axon Reorganization in Epileptic Rats

1999 ◽  
Vol 81 (2) ◽  
pp. 712-721 ◽  
Author(s):  
Paul S. Buckmaster ◽  
F. Edward Dudek
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Molecular Layer ◽  
Axon Collateral ◽  
Cell Axon ◽  
Recurrent Excitation ◽  
The Difference ◽  
Intracellular Analysis

In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. In vivo intracellular recording and labeling in kainate-induced epileptic rats was used to address questions about granule cell axon reorganization in temporal lobe epilepsy. Individually labeled granule cells were reconstructed three dimensionally and in their entirety. Compared with controls, granule cells in epileptic rats had longer average axon length per cell; the difference was significant in all strata of the dentate gyrus including the hilus. In epileptic rats, at least one-third of the granule cells extended an aberrant axon collateral into the molecular layer. Axon projections into the molecular layer had an average summed length of 1 mm per cell and spanned 600 μm of the septotemporal axis of the hippocampus—a distance within the normal span of granule cell axon collaterals. These findings in vivo confirm results from previous in vitro studies. Surprisingly, 12% of the granule cells in epileptic rats, and none in controls, extended a basal dendrite into the hilus, providing another route for recurrent excitation. Consistent with recurrent excitation, many granule cells (56%) in epileptic rats displayed a long-latency depolarization superimposed on a normal inhibitory postsynaptic potential. These findings demonstrate changes, occurring at the single-cell level after an epileptogenic hippocampal injury, that could result in novel, local, recurrent circuits.

Cerebellar Grafts Partially Reverse Amino Acid Receptor Changes Observed in the Cerebellum of Mice with Hereditary Ataxia: Quantitative Autoradiographic Studies

1997 ◽  
Vol 6 (3) ◽  
pp. 347-359
Author(s):  
Kalliope Stasi ◽  
Adamantia Mitsacos ◽  
Lazaros C. Triarhou ◽  
Elias D. Kouvelas
Keyword(s):  
Nmda Receptors ◽  
Cerebellar Cortex ◽  
Binding Sites ◽  
Molecular Layer ◽  
Cerebellar Nuclei ◽  
Granule Cell Layer ◽  
Wild Type ◽  
Hereditary Ataxia ◽  
Deep Cerebellar Nuclei ◽  
Muscimol Binding

We used quantitative autoradiography of [3H]CNQX (200 nM), [3H]muscimol (13 nM), and [3H]flunitrazepam (10 nM) binding to study the distribution of non-NMDA and GABAA receptors in the cerebellum of pcd mutant mice with unilateral cerebellar grafts. Nonspecific binding was determined by incubation with 1 mM Glu, 200 μM GABA, or 1 μM clonazepam, respectively. Saturation parameters were defined in wild-type and mutant cerebella. In mutants, non-NMDA receptors were reduced by 38% in the molecular layer and by 47% in the granule cell layer. The reduction of non-NMDA receptors in the pcd cerebellar cortex supports their localization on Purkinje cells. [3H] CNQX binding sites were visualized at higher density in grafts that had migrated to the cerebellar cortex of the hosts (4.1 and 11.0 pmol/mg protein, respectively, at 23 and 37 days after grafting) than in grafts arrested intraparen-chymally (2.6 and 6.2 pmol/mg protein, respectively, at 23 and 37 days after grafting). The pattern of expression of non-NMDA receptors in cortical vs. parenchymal grafts suggests a possible regulation of their levels by transacting elements from host parallel fibers. GABAA binding levels in the grafts for both ligands used were similar to normal molecular layer. Binding was increased in the deep cerebellar nuclei of pcd mutants: the increase in [3H]muscimol binding over normal was 215% and the increase in [3H]flunitrazepam binding was 89%. Such increases in the pcd deep cerebellar nuclei may reflect a denervation-induced supersensitivity subsequent to the loss of Purkinje axon terminal innervation. In the deep nuclei of pcd mutants with unilateral cerebellar grafts, [3H]muscimol binding was 31% lower in the grafted side than in the contralateral nongrafted side at 37 days after transplantation; [3H]fluni-trazepam binding was also lower in the grafted side by 15% compared to the nongrafted side. Such changes in GABAA receptors suggest a significant, albeit partial, normalizing trend of cerebellar grafts on the state of postsynaptic supersensitive receptors in the host cerebellar nuclei.

Optical Recording Study of Granule Cell Activities in the Hippocampal Dentate Gyrus of Kainate-Treated Rats

2000 ◽  
Vol 83 (4) ◽  
pp. 2421-2430 ◽  
Author(s):  
Yo Otsu ◽  
Eiichi Maru ◽  
Hisayuki Ohata ◽  
Ichiro Takashima ◽  
Riichi Kajiwara ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Mossy Fibers ◽  
Optical Recording ◽  
Granule Cell Layer ◽  
Gabaergic Inhibition ◽  
Mossy Fiber Sprouting

In the epileptic hippocampus, newly sprouted mossy fibers are considered to form recurrent excitatory connections to granule cells in the dentate gyrus and thereby increase seizure susceptibility. To study the effects of mossy fiber sprouting on neural activity in individual lamellae of the dentate gyrus, we used high-speed optical recording to record signals from voltage-sensitive dye in hippocampal slices prepared from kainate-treated epileptic rats (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a large depolarization in almost the entire molecular layer in which granule cell apical dendrites are located. The signals were identified as postsynaptic responses because of their dependence on extracellular Ca2+. The depolarization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the granule cell layer. In the inner molecular layer, a good correlation was obtained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicuculline enlarged the depolarization in granule cell dendrites. Our data indicate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAergic inhibition partly masks the synaptic depolarization. However, despite the large dendritic excitation induced by the sprouted mossy fibers, seizurelike activity of granule cells was never observed, even when GABAergic inhibition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.

pH Sensitivity of Non-Synaptic Field Bursts in the Dentate Gyrus

2000 ◽  
Vol 84 (2) ◽  
pp. 927-933 ◽  
Author(s):  
Jeffrey S. Schweitzer ◽  
Haiwei Wang ◽  
Zhi-Qi Xiong ◽  
Janet L. Stringer
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Granule Cell ◽  
Low Ph ◽  
Ph Sensitivity ◽  
Extracellular Ph ◽  
Granule Cell Layer ◽  
Ph Changes

Under conditions of low [Ca2+]o and high [K+]o, the rat dentate granule cell layer in vitro develops recurrent spontaneous prolonged field bursts that resemble an in vivo phenomenon called maximal dentate activation. To understand how pH changes in vivo might affect this phenomenon, the slices were exposed to different extracellular pH environments in vitro. The field bursts were highly sensitive to extracellular pH over the range 7.0–7.6 and were suppressed at low pH and enhanced at high pH. Granule cell resting membrane potential, action potentials, and postsynaptic potentials were not significantly altered by pH changes within the range that suppressed the bursts. The pH sensitivity of the bursts was not altered by pharmacologic blockade of N-methyl-d-aspartate (NMDA), non-NMDA, and GABAA receptors at concentrations of these agents sufficient to eliminate both spontaneous and evoked synaptic potentials. Gap junction patency is known to be sensitive to pH, and agents that block gap junctions, including octanol, oleamide, and carbenoxolone, blocked the prolonged field bursts in a manner similar to low pH. Perfusion with gap junction blockers or acidic pH suppressed field bursts but did not block spontaneous firing of single and multiple units, including burst firing. These data suggest that the pH sensitivity of seizures and epileptiform phenomena in vivo may be mediated in large part through mechanisms other than suppression of NMDA-mediated or other excitatory synaptic transmission. Alterations in electrotonic coupling via gap junctions, affecting field synchronization, may be one such process.

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