Granular Layer Neurons Control Cerebellar Neurovascular Coupling Through an NMDA Receptor/NO-Dependent System

Mapelli, Lisa; Gagliano, Giuseppe; Soda, Teresa; Laforenza, Umberto; Moccia, Francesco; D’Angelo, Egidio

doi:10.1523/jneurosci.2025-16.2016

Cited by 71 publications

(84 citation statements)

References 80 publications

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“…To validate this preliminary information at protein level, we carried out immunohistochemistry on the rat cerebellar granular layer by using a rabbit polyclonal antibody raised against the N-terminal domain of human TRPM4 (Kim et al, 2013). GrCs were identified by co-staining the slices with DAPI, as recently described in (Mapelli et al, 2017). Confocal microscopy revealed that TRPM4 protein was expressed in GrCs both on the plasma membrane and within the cytosol (Fig.…”

Section: Trp Current Expression In Accelerating Grcsmentioning

confidence: 88%

Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage

Masoli¹,

Marialuisa²,

Laforenza

et al. 2019

Preprint

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The cerebellar granule cells (GrCs) form an anatomically homogeneous neuronal population which, in its canonical description, discharges regularly without adaptation. We show here that GrCs in fact generate diverse response patterns to current injection and synaptic activation, ranging from adaptation to acceleration of firing. Adaptation was predicted by parameter optimization in detailed GrC computational models based on the available knowledge on GrC ionic channels. The models also predicted that acceleration required the involvement of additional mechanisms. We found that yet unrecognized TRPM4 currents in accelerating GrCs could specifically account for firing acceleration. Moreover, adapting GrCs were better in transmitting high-frequency mossy fiber (MF) bursts over a background discharge than accelerating GrCs. This implied that different electroresponsive patterns corresponded to specific synaptic properties reflecting different neurotransmitter release probability. The correspondence of pre-and post-synaptic properties generated effective MF-GrC transmission channels, which could enrich the processing of input spike patterns and enhance spatio-temporal recoding at the cerebellar input stage.

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Section: Trp Current Expression In Accelerating Grcsmentioning

confidence: 88%

Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage

Masoli¹,

Marialuisa²,

Laforenza

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some researchers even argue that capillary flow is regulated by contractile pericytes on first and second order capillaries (Peppiatt et al, 2006;Hall et al, 2014;Mishra et al, 2016;Khennouf et al, 2018). Mechanisms involved in neurovascular coupling tend to vary by the signaling cell type and location within the brain (Devonshire et al, 2012;Uhlirova et al, 2016;Mapelli et al, 2017). Furthermore, the relative importance of each pathway in producing functional hyperemia is still in question (Attwell et al, 2010;Iadecola, 2017;Longden et al, 2017;Mapelli et al, 2017;Hogan-Cann et al, 2019).…”

Section: Regulation Of Cerebral Blood Flow and Neurovascular Couplingmentioning

confidence: 99%

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

Schager

Brown

2020

J Cereb Blood Flow Metab

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Vessel loss in the aging brain is commonly reported, yet important questions remain concerning whether there are regional vulnerabilities and what mechanisms could account for these regional differences, if they exist. Here we imaged and quantified vessel length, tortuosity and width in 15 brain regions in young adult and aged mice. Our data indicate that vessel loss was most pronounced in white matter followed by cortical, then subcortical grey matter regions, while some regions (visual cortex, amygdala, thalamus) showed no decline with aging. Regions supplied by the anterior cerebral artery were more vulnerable to loss than those supplied by middle or posterior cerebral arteries. Vessel width and tortuosity generally increased with age but neither reliably predicted regional vessel loss. Since capillaries are naturally prone to plugging and prolonged obstructions often lead to vessel pruning, we hypothesized that regional susceptibilities to plugging could help predict vessel loss. By mapping the distribution of microsphere-induced capillary obstructions, we discovered that regions with a higher density of persistent obstructions were more likely to show vessel loss with aging and vice versa. These findings indicate that age-related vessel loss is region specific and can be explained, at least partially, by regional susceptibilities to capillary plugging.

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“…It has been found that capillary dilation occurs following the effect on pericytes of E2 prostaglandins, released by astrocytes, whereas arteriolar dilation occurs following the effect of nitric oxide (NO) released by inter-neurons. Furthermore, the dilation of capillaries by pericytes occurs faster than that of arterioles and offers a greater increase in blood flow [37]. Moreover, the effect of NO, released by the neurons of the granular layer, is two-fold, in that, in addition to causing vasodilation, it inhibits the synthesis of the powerful vasoconstrictor 20-Hydroxyeicosatetraenoic acid (20-HETE), which is produced in pericytes by the metabolism of arachidonic acid [38].…”

Section: Blood Flow Regulationmentioning

confidence: 99%

Pericytes in Microvessels: From “Mural” Function to Brain and Retina Regeneration

Caporarello

D’Angeli

Cambria

et al. 2019

IJMS

101

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Pericytes are branched cells located in the wall of capillary blood vessels that are found throughout the body, embedded within the microvascular basement membrane and wrapping endothelial cells, with which they establish a strong physical contact. Pericytes regulate angiogenesis, vessel stabilization, and contribute to the formation of both the blood-brain and blood-retina barriers by Angiopoietin-1/Tie-2, platelet derived growth factor (PDGF) and transforming growth factor (TGF) signaling pathways, regulating pericyte-endothelial cell communication. Human pericytes that have been cultured for a long period give rise to multilineage progenitor cells and exhibit mesenchymal stem cell (MSC) features. We focused our attention on the roles of pericytes in brain and ocular diseases. In particular, pericyte involvement in brain ischemia, brain tumors, diabetic retinopathy, and uveal melanoma is described. Several molecules, such as adenosine and nitric oxide, are responsible for pericyte shrinkage during ischemia-reperfusion. Anti-inflammatory molecules, such as IL-10, TGFβ, and MHC-II, which are increased in glioblastoma-activated pericytes, are responsible for tumor growth. As regards the eye, pericytes play a role not only in ocular vessel stabilization, but also as a stem cell niche that contributes to regenerative processes in diabetic retinopathy. Moreover, pericytes participate in melanoma cell extravasation and the genetic ablation of the PDGF receptor reduces the number of pericytes and aberrant tumor microvessel formation with important implications for therapy efficacy. Thanks to their MSC features, pericytes could be considered excellent candidates to promote nervous tissue repair and for regenerative medicine.

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Granular Layer Neurons Control Cerebellar Neurovascular Coupling Through an NMDA Receptor/NO-Dependent System

Cited by 71 publications

References 80 publications

Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage

Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

Pericytes in Microvessels: From “Mural” Function to Brain and Retina Regeneration

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