Influence of experimentally induced agranularity on the synaptogenesis of serotonin nerve terminals in rat cerebellar cortex

1979 ◽  
Vol 206 (1162) ◽  
pp. 133-138 ◽  
Keyword(s):  
Cerebellar Cortex ◽  
Granular Layer ◽  
Granule Cells ◽  
Absolute Number ◽  
External Granular Layer ◽  
X Ray ◽  
Synaptic Contacts ◽  
Cellular Environment ◽  
Normal Controls ◽  
Synaptic Remodelling

The serotonin (5-HT) innervation of the posterior vermis was studied by high resolution radioautography in both normal and X-ray-induced agranular rat cerebella, following 3 h topical superfusion with 10 -4 M 3 H-5-HT. In the normal cerebellar cortex, 5-HT axonal varicosities are scarce and only rarely exhibit the membrane differentiations character­izing synaptic contacts. In the agranular cerebellum, 5-HT terminals ap­pear to have a much higher density than in normal controls, although their absolute number may not be significantly different when the import­ant reduction in volume of this experimental cerebellum is taken into account. These terminals frequently show typical synaptic contacts. Most of them are established on the branchlet spines of Purkinje cell dendrites, but some are also observed on the shafts of Golgi cell dendrites. The 5-HT innervation of the cerebellar cortex thus undergoes important changes in the absence of granule cells. It is suggested that these modifications may be part of the general reorganization process of the cerebellar circuitry consequent on the early destruction of the external granular layer. This new example of synaptic remodelling could imply that the formation of cerebellar connectivity is modulated, to a certain extent, by the local cellular environment.

Cerebellar Granule Cells and Their Response to Radiation

1970 ◽  
Vol 28 ◽  
pp. 212-213
Author(s):  
Rosita F. de Estable-Puig ◽  
Juan F. Estable-Puig
Keyword(s):  
Cerebellar Cortex ◽  
Granular Layer ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Synaptic Connections ◽  
Cerebellar Granule ◽  
Peripheral Axon ◽  
Cerebellar Glomerulus

The granular layer of the cerebellar cortex situated between the molecular and medullary layers is built up mainly of the perikarya of small interneurons, the granule cells intermingled with part of their own processes, mossy fiber terminals, fibers of passage and other less numerous intrinsic cells. Ultrastructurally they are characterized by a nucleus which occupies most of the cell body and a rim of cytoplasm. The nucleus exhibits some aggregates of chromatin and in some cells a nucleolus. In the cytoplasm very scarce organelles are observed (Fig.l). Their main synaptic connections are found, first, at the cerebellar glomerulus where granule dendrites are seen in postsynaptic position towards mossy fiber rosettes. Desmosomic attachments are observed between granule dendrites. Second, at the level of the molecular layer where parallel fiber terminals (ramifications of the peripheral axon ) are seen apposing Purkinje dendrite spines.

Maintenance of Wnt-3 expression in Purkinje cells of the mouse cerebellum depends on interactions with granule cells

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1277-1286 ◽  
Author(s):  
P.C. Salinas ◽  
C. Fletcher ◽  
N.G. Copeland ◽  
N.A. Jenkins ◽  
R. Nusse
Keyword(s):  
Cell Fate ◽  
Purkinje Cells ◽  
Granular Layer ◽  
Simple Structure ◽  
Granule Cells ◽  
Cell Populations ◽  
Specific Cell ◽  
External Granular Layer ◽  
Mouse Mutants ◽  
The Brain

Wnt genes encode secreted proteins implicated in cell fate changes during development. To define specific cell populations in which Wnt genes act, we have examined Wnt expression in the cerebellum. This part of the brain has a relatively simple structure and contains well-characterized cell populations. We found that Wnt-3 is expressed during development of the cerebellum and that expression is restricted to the Purkinje cell layer in the adult. Wnt-3 expression in Purkinje cells increases postnatally as granule cells start to make contacts with Purkinje cells. To investigate whether interactions with granule cells influence Wnt-3 expression in Purkinje cells, we examined gene expression in several mouse mutants, using the expression of En-2 to follow the fate of granule cells. In the weaver mutant, in which granule cells fail to migrate and subsequently die in the external granular layer, Wnt-3 expression was normal at postnatal day 15 (P15). At that time, some granule cells are still present in the external granular layer. At P28, however, when granule cells could no longer be detected, Wnt-3 expression was almost absent. In the meander tail mutant, in which the anterior cerebellar lobes lack granule cells, Wnt-3 expression was only detected in the normal posterior lobes. Since En genes are implicated in cell-cell interactions mediated by Wnt genes, we examined En-2/En-2 mutant mice, finding normal Wnt-3 expression, indicating that the effect of granule cells on the maintenance of Wnt-3 is not mediated by En-2. Our results show that Wnt-3 expression in Purkinje cells is modulated by their presynaptic granule cells at the time of neuronal maturation.

The development of the radial glial scaffold of the cerebellar cortex from GFAP-positive cells in the external granular layer

1994 ◽  
Vol 23 (2) ◽  
pp. 97-115 ◽  
Author(s):  
J. Sievers ◽  
F. W. Pehlemann ◽  
S. Gude ◽  
D. Hartmann ◽  
M. Berry
Keyword(s):  
Cerebellar Cortex ◽  
Granular Layer ◽  
External Granular Layer ◽  
Radial Glial

Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4213-4224
Author(s):  
C.M. Rosario ◽  
B.D. Yandava ◽  
B. Kosaras ◽  
D. Zurakowski ◽  
R.L. Sidman ◽  
...  
Keyword(s):  
Granule Cell ◽  
Granular Layer ◽  
Granule Cells ◽  
Cell Types ◽  
Anterior Lobe ◽  
Neural Progenitors ◽  
Recessive Mutation ◽  
External Granular Layer ◽  
Deficient Cell ◽  
Multipotent Progenitors

Previously we observed that stable clones of multipotent neural progenitor cells, initially isolated and propagated from the external granular layer of newborn wild-type mouse cerebellum, could participate appropriately in cerebellar development when reimplanted into the external granular layer of normal mice. Donor cells could reintegrate and differentiate into neurons (including granule cells) and/or glia consistent with their site of engraftment. These findings suggested that progenitors might be useful for cellular replacement in models of aberrant neural development or neurodegeneration. We tested this hypothesis by implanting clonally related multipotent progenitors into the external granular layer of newborn meander tail mice (gene symbol=mea). mea is an autosomal recessive mutation characterized principally by the failure of granule cells to develop in the cerebellar anterior lobe; the mechanism is unknown. We report that approximately 75% of progenitors transplanted into the granuloprival anterior lobe of neonatal mea mutants differentiated into granule cells, partially replacing or augmenting that largely absent neuronal population in the internal granular layer of the mature meander tail anterior lobe. (The ostensibly ‘normal’ meander tail posterior lobe also benefited from repletion of a more subtle granule cell deficiency.) Donor-derived neurons were well-integrated within the neuropil, suggesting that these progenitors' developmental programs for granule cell differentiation were unperturbed. These observations permitted several conclusions. (1) That exogenous progenitors could survive transplantation into affected regions of neonatal meander tail cerebellum and differentiate into the deficient cell type suggested that the microenvironment was not inimical to granule cell development. Rather it suggested that mea's deleterious action is intrinsic to the external granular layer cell. (Any cell-extrinsic actions--albeit unlikely--had to be restricted to readily circumventable prenatal events.) This study, therefore, offers a paradigm for using progenitors to help determine the site of action of other mutant genes or to test hypotheses regarding the pathophysiology underlying other anomalies. (2) In the regions most deficient in neurons, a neuronal phenotype was pursued in preference to other potential cell types, suggesting a ‘push’ of undifferentiated, multipotent progenitors towards compensation for granule cell dearth. These data suggested that progenitors with the potential for multiple fates might differentiate towards repletion of deficient cell types, a possible developmental mechanism with therapeutic implications. Neural progenitors (donor or endogenous) might enable cell replacement in some developmental or degenerative diseases--most obviously in cases where a defect is intrinsic to the diseased cell, but also, under certain circumstances, when extrinsic pathologic forces may exist.

scholarly journals Accounting for uncertainty: inhibition for neural inference in the cerebellum

2021 ◽  
Vol 288 (1947) ◽  
Author(s):  
Ensor Rafael Palacios ◽  
Conor Houghton ◽  
Paul Chadderton
Keyword(s):  
State Estimation ◽  
Cerebellar Cortex ◽  
Granular Layer ◽  
Granule Cells ◽  
Neural Mechanisms ◽  
Golgi Cell ◽  
Golgi Cells ◽  
Neural Representations ◽  
Cell Inhibition ◽  
Specific Contribution

Sensorimotor coordination is thought to rely on cerebellar-based internal models for state estimation, but the underlying neural mechanisms and specific contribution of the cerebellar components is unknown. A central aspect of any inferential process is the representation of uncertainty or conversely precision characterizing the ensuing estimates. Here, we discuss the possible contribution of inhibition to the encoding of precision of neural representations in the granular layer of the cerebellar cortex. Within this layer, Golgi cells influence excitatory granule cells, and their action is critical in shaping information transmission downstream to Purkinje cells. In this review, we equate the ensuing excitation–inhibition balance in the granular layer with the outcome of a precision-weighted inferential process, and highlight the physiological characteristics of Golgi cell inhibition that are consistent with such computations.

scholarly journals Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum

2021 ◽  
Vol 14 ◽  
Author(s):  
G. Giacomo Consalez ◽  
Daniel Goldowitz ◽  
Filippo Casoni ◽  
Richard Hawkes
Keyword(s):  
Granular Layer ◽  
Granule Cells ◽  
Review Article ◽  
Cell Type ◽  
External Granular Layer ◽  
Homogeneous Population ◽  
Multiple Phenotypes ◽  
Numerous Cell ◽  
Rhombic Lip ◽  
The Brain

Granule cells (GCs) are the most numerous cell type in the cerebellum and indeed, in the brain: at least 99% of all cerebellar neurons are granule cells. In this review article, we first consider the formation of the upper rhombic lip, from which all granule cell precursors arise, and the way by which the upper rhombic lip generates the external granular layer, a secondary germinal epithelium that serves to amplify the upper rhombic lip precursors. Next, we review the mechanisms by which postmitotic granule cells are generated in the external granular layer and migrate radially to settle in the granular layer. In addition, we review the evidence that far from being a homogeneous population, granule cells come in multiple phenotypes with distinct topographical distributions and consider ways in which the heterogeneity of granule cells might arise during development.

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