Interactions Between Purkinje Cells and Granule Cells Coordinate the Development of Functional Cerebellar Circuits

Heijden, Meike E van der; Sillitoe, Roy V.

doi:10.1016/j.neuroscience.2020.06.010

Cited by 42 publications

(37 citation statements)

References 198 publications

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“…Finally, whereas each Purkinje cell is initially innervated by multiple climbing fibers, originating in the inferior olive, it is the granule cell input on the Purkinje cell dendritic tree that contributes to the pruning of supernumerary inputs until each Purkinje cell receives input from precisely one climbing fiber. Strikingly, in humans, these processes start before the third trimester begins and con-tinue until up to two years after birth (detailed reviews on cerebellar development in [10][11][12]). Altogether, the cerebellum initiates a remarkable set of processes including dynamic changes in its size, morphology, and synaptic arrangements during the later stages of prenatal development.…”

Section: Development Of the Cerebellar Circuitmentioning

confidence: 99%

“…Cerebellar development follows a protracted developmental timeline compared to the cerebral cortex [11, 12, 28]. The first cerebellar neurons are born during mid embryogenesis, but neurogenesis and differentiation of the late-born granule cells, which are the most populous cell type in the brain, occurs during gestational weeks 20–40 in humans and postnatally in rodents (shown in Fig.…”

Section: Development Of the Cerebellar Circuitmentioning

confidence: 99%

“…As the survival of these prematurely born infants has increased significantly in the last 2 decades, the greater risk for ASD has been exposed and studied in more depth. Preterm birth and cerebellar hemorrhage coincide with, and may specifically disrupt, the period of highly dynamic cerebellar development that is characterized by morphologic and synaptic reorganization [10][11][12]. These findings have led researchers to hypothesize that there may be a developmental time window during which the cerebellum is central for the acquisition of cognitive function and social skills [13].…”

Section: Introductionmentioning

confidence: 99%

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Abnormal Cerebellar Development in Autism Spectrum Disorders

2021

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Autism spectrum disorders (ASD) comprise a group of heterogeneous neurodevelopmental conditions characterized by impaired social interactions and repetitive behaviors with symptom onset in early infancy. The genetic risks for ASD have long been appreciated: concordance of ASD diagnosis may be as high as 90% for monozygotic twins and 30% for dizygotic twins, and hundreds of mutations in single genes have been associated with ASD. Nevertheless, only 5–30% of ASD cases can be explained by a known genetic cause, suggesting that genetics is not the only factor at play. More recently, several studies reported that up to 40% of infants with cerebellar hemorrhages and lesions are diagnosed with ASD. These hemorrhages are overrepresented in severely premature infants, who are born during a period of highly dynamic cerebellar development that encompasses an approximately 5-fold size expansion, an increase in structural complexity, and remarkable rearrangements of local neural circuits. The incidence of ASD-causing cerebellar hemorrhages during this window supports the hypothesis that abnormal cerebellar development may be a primary risk factor for ASD. However, the links between developmental deficits in the cerebellum and the neurological dysfunctions underlying ASD are not completely understood. Here, we discuss key processes in cerebellar development, what happens to the cerebellar circuit when development is interrupted, and how impaired cerebellar function leads to social and cognitive impairments. We explore a central question: Is cerebellar development important for the generation of the social and cognitive brain or is the cerebellum part of the social and cognitive brain itself?

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Section: Development Of the Cerebellar Circuitmentioning

confidence: 99%

Section: Development Of the Cerebellar Circuitmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Abnormal Cerebellar Development in Autism Spectrum Disorders

2021

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“…The endogenous concentration of DHA and DHA supplementation via milk positively correlate with the short-term cognitive performance of preterm infants [19][20][21][22]. The cerebellar granule cells establish firing properties of Purkinje cells, which provide the only output from the cerebellar cortex [47]. The cerebellum is involved in cognition [48], and two-photon calcium imaging revealed that granule cells convey information about the expectation of reward [49].…”

Section: Discussionmentioning

confidence: 99%

Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

2020

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Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development.

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“…Moreover, they are concentrated in synaptic terminals of Purkinje cells while PMCA1 and PMCA4 localize mostly to granular layer [ 91 ]. Purkinje cells integrate the excitatory input to the cerebellar cortex being an essential component for the regulation and coordination of motor movements [ 92 ]. It is therefore not surprising that one of the most visible cerebellar dysfunctions during ataxia are uncoordinated movements and inability to maintain body balance.…”

Section: Plasma Membrane Ca 2+ -Atpase (Pmca)—tmentioning

confidence: 99%

Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

Boczek

Sobolczyk

Mackiewicz

et al. 2021

IJMS

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Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca2+ signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca2+, neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca2+-ATPase (PMCA), sarco/endoplasmic Ca2+-ATPase (SERCA) and secretory pathway Ca2+-ATPase (SPCA) are considered efficient line of defense against abnormal Ca2+ rises. However, their role is not limited only to Ca2+ transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca2+-ATPases to neuropathology, with a special emphasis on mental diseases.

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Interactions Between Purkinje Cells and Granule Cells Coordinate the Development of Functional Cerebellar Circuits

Cited by 42 publications

References 198 publications

Abnormal Cerebellar Development in Autism Spectrum Disorders

Abnormal Cerebellar Development in Autism Spectrum Disorders

Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs

Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

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