Regionally Specific Distribution of Corticospinal Synapses Because of Activity-Dependent Synapse Elimination In Vitro

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.

Download Full-text

Arc/Arg3.1 Is a Postsynaptic Mediator of Activity-Dependent Synapse Elimination in the Developing Cerebellum

Neuron ◽

10.1016/j.neuron.2013.04.036 ◽

2013 ◽

Vol 78 (6) ◽

pp. 1024-1035 ◽

Cited By ~ 60

Author(s):

Takayasu Mikuni ◽

Naofumi Uesaka ◽

Hiroyuki Okuno ◽

Hirokazu Hirai ◽

Karl Deisseroth ◽

...

Keyword(s):

Synapse Elimination ◽

Developing Cerebellum ◽

Activity Dependent

Download Full-text

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

10.21203/rs.3.rs-59368/v1 ◽

2020 ◽

Author(s):

Amparo López-Carrasco ◽

Susana Martín-Vañó ◽

Rebeca Burgos-Panadero ◽

Ezequiel Monferrer ◽

Ana P Berbegall ◽

...

Keyword(s):

Extracellular Matrix ◽

High Risk ◽

Cell Lines ◽

Neuroblastoma Cell ◽

Chromosome 9 ◽

Future Research ◽

Knock Out ◽

Specific Distribution

Abstract Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We have applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN amplified SK-N-BE(2) and the ALK mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of both cell lines are affected. Results We describe a remarkable subclonal selection of some genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. Specially, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. Genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

Download Full-text

Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex

eLife ◽

10.7554/elife.09862 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 33

Author(s):

Antoine M Valera ◽

Francesca Binda ◽

Sophie A Pawlowski ◽

Jean-Luc Dupont ◽

Jean-François Casella ◽

...

Keyword(s):

Purkinje Cells ◽

Cerebellar Cortex ◽

Granule Cell ◽

Motor Coordination ◽

Molecular Layer ◽

Granule Cell Layer ◽

Synaptic Organization ◽

Cerebellar Modules ◽

Activity Dependent

Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex.

Download Full-text