Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum

Kim, Taegon; Park, Heeyoun; Tanaka-Yamamoto, Keiko; Yamamoto, Yukio

doi:10.1038/s42003-023-04825-y

Cited by 4 publications

(1 citation statement)

References 56 publications

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“…Axonal fibers of GCs that receive MF input make initially contact with the soma of PCs, but around P5-P15 they start to turn into the typical parallel fibers that establish synaptic contacts with the dendrites of PCs [80]. PCs and GCs generate their zonal circuit map early during development [90].…”

Section: Embryology Of the Precerebellar Systemmentioning

confidence: 99%

Critical Periods and Vulnerability of Cerebellar Development in Human and Rodent

Westerhuis,

Dudink,

De Zeeuw

et al. 2024

Preprint

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A significant percentage of children suffer from neurodevelopmental aberrations, which have long-term effects on both individuals and society. Since the developmental timelines of different brain regions vary, the type, severity and timing of harmful exposures are crucial for understanding the specific pathological processes and consequences involved. During development, the cerebellum is one of the first brain structures to begin to differentiate, but one of the last to achieve maturity. This relatively long period underscores its vulnerability to detrimental environmental exposures throughout gestation. Moreover, as the postnatal functionality of the cerebellum is multifaceted, enveloping sensorimotor, cognitive, and emotional domains, prenatal disruptions in cerebellar development can result in a variety of neurological and mental health disorders. Here, we review major intrauterine insults that affect cerebellar development in both humans and rodents, ranging from abuse of toxic chemical agents such as alcohol and nicotine, to stress and sleep, malnutrition as well as infections. Understanding these pathological mechanisms in the context of the different stages of cerebellar development in humans and rodents may help us to identify critical and vulnerable periods and thereby to prevent the risk of associated prenatal and early postnatal damage that can lead to lifelong neurological and cognitive disabilities.

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Section: Embryology Of the Precerebellar Systemmentioning

confidence: 99%

Critical Periods and Vulnerability of Cerebellar Development in Human and Rodent

Westerhuis,

Dudink,

De Zeeuw

et al. 2024

Preprint

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Reduced Cerebellar BDNF Availability Affects Postnatal Differentiation and Maturation of Granule Cells in a Mouse Model of Cholesterol Dyshomeostasis

et al. 2023

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Niemann-Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder due to mutations in the NPC1 gene resulting in the accumulation of cholesterol within the endosomal/lysosomal compartments. The prominent feature of the disorder is the progressive Purkinje cell degeneration leading to ataxia.In a mouse model of NPC1 disease, we have previously demonstrated that impaired Sonic hedgehog signaling causes defective proliferation of granule cells (GCs) and abnormal cerebellar morphogenesis. Studies conducted on cortical and hippocampal neurons indicate a functional interaction between Sonic hedgehog and brain-derived neurotrophic factor (BDNF) expression, leading us to hypothesize that BDNF signaling may be altered in Npc1 mutant mice, contributing to the onset of cerebellar alterations present in NPC1 disease before the appearance of signs of ataxia.We characterized the expression/localization patterns of the BDNF and its receptor, tropomyosin-related kinase B (TrkB), in the early postnatal and young adult cerebellum of the Npc1nmf164 mutant mouse strain.In Npc1nmf164 mice, our results show (i) a reduced expression of cerebellar BDNF and pTrkB in the first 2 weeks postpartum, phases in which most GCs complete the proliferative/migrative program and begin differentiation; (ii) an altered subcellular localization of the pTrkB receptor in GCs, both in vivo and in vitro; (iii) reduced chemotactic response to BDNF in GCs cultured in vitro, associated with impaired internalization of the activated TrkB receptor; (iv) an overall increase in dendritic branching in mature GCs, resulting in impaired differentiation of the cerebellar glomeruli, the major synaptic complex between GCs and mossy fibers.

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Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells

Jun,

Kim,

Park

et al. 2023

Cell Reports

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Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum

Cited by 4 publications

References 56 publications

Critical Periods and Vulnerability of Cerebellar Development in Human and Rodent

Critical Periods and Vulnerability of Cerebellar Development in Human and Rodent

Reduced Cerebellar BDNF Availability Affects Postnatal Differentiation and Maturation of Granule Cells in a Mouse Model of Cholesterol Dyshomeostasis

Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells

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