Ultrasturcture of cerebellar cells and neuropil in rats subjected to partial global cerebral ischemia

Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros

Although a previous study in this laboratory determined that Purkinje cells of the rat cerebellum did not appear to be damaged following 30 min of forebrain ischemia followed by 30 min of reperfusion, it was suggested that an increase in rough endoplasmic reticulum (RER) and/or polysomes had occurred in these cells. The primary objective of the present study was to morphometrically determine whether or not this increase had occurred. In addition, since there is substantial evidence that glial cells may be affected by ischemia earlier than other cell types, glial cells also were examined. To ascertain possible effects on other cerebellar components, granule cells and neuropil near Purkinje cells as well as neuropil in the molecular layer also were evaluated in this investigation.

Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros

In severe cerebral ischemia, Purkinje cells of the cerebellum are one of the cell types most vulnerable to anoxic damage. In the partial (forebrain) global ischemic (PGI) model of the rat, Paljärvi noted at the light microscopic level that cerebellar damage is inconsistant and when present, milder than in the telencephalon, diencephalon and rostral brain stem. Cerebellar injury was observed in 3 of 4 PGI rats following 5 minutes of reperfusion but in none of the rats after 90 min of reperfusion. To evaluate a time between these two extremes (5 and 90 min), the present investigation used the PGI model to study the effects of ischemia on the ultrastructure of cerebellar Purkinje cells in rats that were sacrificed after 30 min of reperfusion. This time also was chosen because lactic acid that is thought to contribute to ischemic cell changes in PGI is at a maximum after 30 min of reperfusion.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abdelraheim H. Attaai ◽  
Ahmed E. Noreldin ◽  
Fatma M. Abdel-maksoud ◽  
Manal T. Hussein

AbstractStudying the cerebella of different animals is important to expand the knowledge about the cerebellum. Studying the camel cerebellum was neglected even though the recent research in the middle east and Asia. Therefore, the present study was designed to achieve a detailed description of the morphology and the cellular organization of the camel cerebellum. Because of the high importance of the calcium ions as a necessary moderator the current work also aimed to investigate the distribution of calcium binding proteins (CaBP) such as calbindin D-28K (CB), parvalbumin (PV) and calretinin (CR) in different cerebellar cells including the non-traditional neurons. The architecture of camel cerebellum, as different mammals, consists of the medulla and three layered-cortex. According to our observation the cells in the granular layer were not crowded and many spaces were observed. CB expression was the highest by Purkinje cells including their dendritic arborization. In addition to its expression by the inhibitory interneurons (basket, stellate and Golgi neurons), it is also expressed by the excitatory granule cells. PV was expressed by Purkinje cells, including their primary arborization, and by the molecular layer cells. CR immunoreactivity (-ir) was obvious in almost all cell layers with varying degrees, however a weak or any expression by the Purkinje cells. The molecular layer cells and the Golgi and the non traditional large neurons of the granular layer showed the strongest CR-ir. Granule neurons showed moderate immunoreactivity for CB and CR. In conclusion, the results of the current study achieved a complete map for the neurochemical organization of CaBP expression and distribution by different cells in the camel cerebellum.


2018 ◽  
Author(s):  
Ryan T. Willett ◽  
Alexandre Wojcinski ◽  
N. Sumru Bayin ◽  
Zhimin Lao ◽  
Daniel Stephen ◽  
...  

AbstractEfficient function of neural systems requires the production of specific cell types in the correct proportions. Here we report that reduction of the earliest born neurons of the cerebellum, excitatory cerebellar nuclei neurons (eCN), results in a subsequent reduction in growth of the cerebellar cortex due to an accompanying loss of their presynaptic target Purkinje cells. Conditional knockout of the homeobox genes En1 and En2 (En1/2) in the rhombic lip-derived eCN and granule cell precursors leads to embryonic loss of a subset of medial eCN and cell non-autonomous and location specific loss of Purkinje cells, with subsequent proportional scaling down of cortex growth. We propose that subsets of eCN dictate the survival of their specific Purkinje cell partners, and in turn sonic hedgehog secreted by Purkinje cells scales the expansion of granule cells and interneurons to produce functional local circuits and the proper folded morphology of the cerebellum.


2020 ◽  
Author(s):  
Yukari H. Takeo ◽  
S. Andrew Shuster ◽  
Linnie Jiang ◽  
Miley Hu ◽  
David J. Luginbuhl ◽  
...  

SUMMARYThe synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.


1998 ◽  
Vol 80 (6) ◽  
pp. 2860-2869 ◽  
Author(s):  
T. M. Gao ◽  
E. M. Howard ◽  
Z. C. Xu

Gao, T. M., E. M. Howard, and Z. C. Xu. Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo. J. Neurophysiol. 80: 2860–2869, 1998. The spontaneous activities, evoked synaptic responses, and membrane properties of CA3 pyramidal neurons and dentate granule cells in rat hippocampus were compared before ischemia and ≤7 days after reperfusion with intracellular recording and staining techniques in vivo. A four-vessel occlusion method was used to induce ∼14 min of ischemic depolarization. No significant change in spontaneous firing rate was observed in both cell types after reperfusion. The amplitude and slope of excitatory postsynaptic potentials (EPSPs) in CA3 neurons decreased to 50% of control values during the first 12 h reperfusion and returned to preischemic levels 24 h after reperfusion. The amplitude and slope of EPSPs in granule cells slightly decreased 24–36 h after reperfusion. The amplitude of inhibitory postsynaptic potentials in CA3 neurons transiently increased 24 h after reperfusion, whereas that in granule cells showed a transient decrease 24–36 h after reperfusion. The duration of spike width of CA3 and granule cells became longer than that of control values during the first 12 h reperfusion. The spike threshold of both cell types significantly increased 24–36 h after reperfusion, whereas the frequency of repetitive firing evoked by depolarizing current pulse was decreased during this period. No significant change in rheobase and input resistance was observed in CA3 neurons. A transient increase in rheobase and a transient decrease in input resistance were detected in granule cells 24–36 h after reperfusion. The amplitude of fast afterhyperpolarization in both cell types increased for 2 days after ischemia and returned to normal values 7 days after reperfusion. The results from this study indicate that the neuronal excitability and synaptic transmission in CA3 and granule cells are transiently suppressed after severe forebrain ischemia. The depression of synaptic transmission and neuronal excitability may provide protection for neurons after ischemic insult.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Sarah E. Van Dine ◽  
Elsaid Salem ◽  
Elizabeth George ◽  
Nga Yan Siu ◽  
Timothy Dotzler ◽  
...  

Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.


1993 ◽  
Vol 27 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Y. Tago ◽  
O. Katsuta ◽  
M. Tsuchitani

Cerebellar hypoplasia characterized by severe depletion of granule cells and almost intact Purkinje cells was found in a male 19-month-old beagle dog used in a toxicity study. Microscopically, there was a narrow space lacking granule cells between the row of Purkinje cells and the medulla. Gliosis was not seen in any portion of the cerebellum including this space. No significant changes were seen in the Purkinje cells except for occasional cytoplasmic vacuolation. In the molecular layer and medulla, no histopathological abnormalities were observed.


2021 ◽  
Vol 17 (2) ◽  
pp. e1008670
Author(s):  
Yuanhong Tang ◽  
Lingling An ◽  
Ye Yuan ◽  
Qingqi Pei ◽  
Quan Wang ◽  
...  

The dynamics of cerebellar neuronal networks is controlled by the underlying building blocks of neurons and synapses between them. For which, the computation of Purkinje cells (PCs), the only output cells of the cerebellar cortex, is implemented through various types of neural pathways interactively routing excitation and inhibition converged to PCs. Such tuning of excitation and inhibition, coming from the gating of specific pathways as well as short-term plasticity (STP) of the synapses, plays a dominant role in controlling the PC dynamics in terms of firing rate and spike timing. PCs receive cascade feedforward inputs from two major neural pathways: the first one is the feedforward excitatory pathway from granule cells (GCs) to PCs; the second one is the feedforward inhibition pathway from GCs, via molecular layer interneurons (MLIs), to PCs. The GC-PC pathway, together with short-term dynamics of excitatory synapses, has been a focus over past decades, whereas recent experimental evidence shows that MLIs also greatly contribute to controlling PC activity. Therefore, it is expected that the diversity of excitation gated by STP of GC-PC synapses, modulated by strong inhibition from MLI-PC synapses, can promote the computation performed by PCs. However, it remains unclear how these two neural pathways are interacted to modulate PC dynamics. Here using a computational model of PC network installed with these two neural pathways, we addressed this question to investigate the change of PC firing dynamics at the level of single cell and network. We show that the nonlinear characteristics of excitatory STP dynamics can significantly modulate PC spiking dynamics mediated by inhibition. The changes in PC firing rate, firing phase, and temporal spike pattern, are strongly modulated by these two factors in different ways. MLIs mainly contribute to variable delays in the postsynaptic action potentials of PCs while modulated by excitation STP. Notably, the diversity of synchronization and pause response in the PC network is governed not only by the balance of excitation and inhibition, but also by the synaptic STP, depending on input burst patterns. Especially, the pause response shown in the PC network can only emerge with the interaction of both pathways. Together with other recent findings, our results show that the interaction of feedforward pathways of excitation and inhibition, incorporated with synaptic short-term dynamics, can dramatically regulate the PC activities that consequently change the network dynamics of the cerebellar circuit.


2021 ◽  
pp. 1-15
Author(s):  
Eneritz Rueda-Alaña ◽  
Fernando García-Moreno

The cerebellum is a conserved structure of vertebrate brains that develops at the most anterior region of the alar rhombencephalon. All vertebrates display a cerebellum, making it one of the most highly conserved structures of the brain. Although it greatly varies at the morphological level, several lines of research point to strong conservation of its internal neural circuitry. To test the conservation of the cerebellar circuit, we compared the developmental history of the neurons comprising this circuit in three amniote species: mouse, chick, and gecko. We specifically researched the developmental time of generation of the main neuronal types of the cerebellar cortex. This developmental trajectory is known for the mammalian cell types but barely understood for sauropsid species. We show that the neurogenesis of the GABAergic lineage proceeds following the same chronological sequence in the three species compared: Purkinje cells are the first ones generated in the cerebellar cortex, followed by Golgi interneurons of the granule cell layer, and lately by the interneurons of the molecular layer. In the cerebellar glutamatergic lineage, we observed the same conservation of neurogenesis throughout amniotes, and the same vastly prolonged neurogenesis of granule cells, extending much further than for any other brain region. Together these data show that the cerebellar circuitry develops following a tightly conserved chronological sequence of neurogenesis, which is responsible for the preservation of the cerebellum and its function. Our data reinforce the developmental perspective of homology, whereby similarities in neurons and circuits are likely due to similarities in developmental sequence.


Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.


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