Mechanisms Underlying Reorganization of Fractured Tactile Cerebellar Maps After Deafferentation in Developing and Adult Rats

2005 ◽  
Vol 94 (4) ◽  
pp. 2630-2643 ◽  
Author(s):  
Caroly Shumway ◽  
Josée Morissette ◽  
James M. Bower

Our previous studies showed that fractured tactile cerebellar maps in rats reorganize after deafferentation during development and in adulthood while maintaining a fractured somatotopy. Several months after deafferentation of the infraorbital branch of the trigeminal nerve, the missing upper lip innervation is replaced in the tactile maps in the granule cell layer of crus IIa. The predominant input into the denervated area is always the upper incisor representation. This study examined whether this reorganization was caused by mechanisms intrinsic to the cerebellum or extrinsic, i.e., occurring in somatosensory structures afferent to the cerebellum. We first compared normal and deafferented maps and found that the expansion of the upper incisor is not caused by a preexisting bias in the strength or abundance of upper incisor input in normal animals. We then mapped tactile representations before and immediately after denervation. We found that the pattern of reorganization observed in the cerebellum several months later is not caused by unmasking of a silent or weaker upper incisor representation. Both results indicate that the reorganization is not a result of subsequent growth or sprouting mechanism within the cerebellum itself. Finally, we compared postlesion maps in the cerebellum and the somatosensory cortex. We found that the upper incisor representation significantly expands in both regions and that this expansion is correlated, suggesting that reorganization in the cerebellum is a passive consequence of reorganization in afferent cerebellar pathways. This result has important developmental and functional implications.

2011 ◽  
Vol 100 (3) ◽  
pp. 82a
Author(s):  
Don Patrick Bischop ◽  
Céline Roussel ◽  
Serge Schiffmann ◽  
David Gall

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2223-2232 ◽  
Author(s):  
Joshua B. Rubin ◽  
Yoojin Choi ◽  
Rosalind A. Segal

Sonic hedgehog promotes proliferation of developing cerebellar granule cells. As sonic hedgehog is expressed in the cerebellum throughout life it is not clear why proliferation occurs only in the early postnatal period and only in the external granule cell layer. We asked whether heparan sulfate proteoglycans might regulate sonic hedgehog-induced proliferation and thereby contribute to the specialized proliferative environment of the external granule cell layer. We identified a conserved sequence within sonic hedgehog that is essential for binding to heparan sulfate proteoglycans, but not for binding to the receptor patched. Sonic hedgehog interactions with heparan sulfate proteoglycans promote maximal proliferation of postnatal day 6 granule cells. By contrast, proliferation of less mature granule cells is not affected by sonic hedgehog-proteoglycan interactions. The importance of proteoglycans for proliferation increases during development in parallel with increasing expression of the glycosyltransferase genes, exostosin 1 and exostosin 2. These data suggest that heparan sulfate proteoglycans, synthesized by exostosins, may be critical determinants of granule cell proliferation.


Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1435-1442 ◽  
Author(s):  
Paul R. Borghesani ◽  
Jean Michel Peyrin ◽  
Robyn Klein ◽  
Joshua Rubin ◽  
Alexandre R. Carter ◽  
...  

During development of the nervous system, neural progenitors arise in proliferative zones, then exit the cell cycle and migrate away from these zones. Here we show that migration of cerebellar granule cells out of their proliferative zone, the external granule cell layer (EGL), is impaired in Bdnf–/– mice. The reason for impaired migration is that BDNF directly and acutely stimulates granule cell migration. Purified Bdnf–/– granule cells show defects in initiation of migration along glial fibers and in Boyden chamber assays. This phenotype can be rescued by exogenous BDNF. Using time-lapse video microscopy we find that BDNF is acutely motogenic as it stimulates migration of individual granule cells immediately after addition. The stimulation of migration reflects both a chemokinetic and chemotactic effect of BDNF. Collectively, these data demonstrate that BDNF is directly motogenic for granule cells and provides a directional cue promoting migration from the EGL to the internal granule cell layer (IGL). Movies available on-line


2019 ◽  
Vol 25 (6) ◽  
pp. 528-547 ◽  
Author(s):  
Ayda Tavitian ◽  
Wei Song ◽  
Hyman M. Schipper

Hippocampal abnormalities have been heavily implicated in the pathophysiology of schizophrenia. The dentate gyrus of the hippocampus was shown to manifest an immature molecular profile in schizophrenia subjects, as well as in various animal models of the disorder. In this position paper, we advance a hypothesis that this immature molecular profile is accompanied by an identifiable immature morphology of the dentate gyrus granule cell layer. We adduce evidence for arrested maturation of the dentate gyrus in the human schizophrenia-affected brain, as well as multiple rodent models of the disease. Implications of this neurohistopathological signature for current theory regarding the development of schizophrenia are discussed.


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