0000000000054996
AUTHOR
Nicolas Heck
GABAC receptors are functionally expressed in the intermediate zone and regulate radial migration in the embryonic mouse neocortex
Radial neuronal migration in the cerebral cortex depends on trophic factors and the activation of different voltage- and ligand-gated channels. To examine the func- tional role of GABAC receptors in radial migration we ana- lyzed the effects of specific GABAA and GABAC receptor antagonists on the migration of BrdU-labeled neurons in vitro using organotypic neocortical slice cultures. These experi- ments revealed that the GABAA specific inhibitor bicuculline methiodide facilitated neuronal migration, while the GABAC specific inhibitor (1,2,5,6-tetrahydropyridine-4-yl) methylphos- phinic-acid (TPMPA) impeded migration. Co-application of TPMPA and bicuculline methiodide or the unspecific ionot…
GABA-A Receptors Regulate Neocortical Neuronal Migration In Vitro and In Vivo
The cortical migration process depends on a number of trophic factors and on the activation of different voltage- and ligand-gated channels. We investigated the role of gamma-aminobutyric acid (GABA) type A receptors in the neuronal migration process of the newborn rat parietal cortex in vivo and in vitro. Local in vivo application of the GABA-A antagonist bicuculline methiodide (BMI) or the agonist muscimol via cortical surface Elvax implants induced prominent alterations in the cortical architecture when compared with untreated or sham-operated controls. BMI- and muscimol-treated animals revealed heterotopic cell clusters in the upper layers and a complete loss of the cortical lamination …
Activity-Dependent Regulation of Neuronal Apoptosis in Neonatal Mouse Cerebral Cortex
A massive neuronal loss during early postnatal development has been well documented in the murine cerebral cortex, but the factors that drive cells into apoptosis are largely unknown. The role of neuronal activity in developmental apoptosis was studied in organotypic neocortical slice cultures of newborn mice. Multielectrode array and whole-cell patch-clamp recordings revealed spontaneous network activity characterized by synchronized burst discharges, which could be blocked by tetrodotoxin and ionotropic glutamate receptor antagonists. The identical neuropharmacological manipulations also caused a significant increase in the number of apoptotic neurons as early as 6 h after the start of dr…
DSD-1-Proteoglycan/Phosphacan and Receptor Protein Tyrosine Phosphatase-Beta Isoforms during Development and Regeneration of Neural Tissues
Interactions between neurons and glial cells play important roles in regulating key events of development and regeneration of the CNS. Thus, migrating neurons are partly guided by radial glia to their target, and glial scaffolds direct the growth and directional choice of advancing axons, e.g., at the midline. In the adult, reactive astrocytes and myelin components play a pivotal role in the inhibition of regeneration. The past years have shown that astrocytic functions are mediated on the molecular level by extracellular matrix components, which include various glycoproteins and proteoglycans. One important, developmentally regulated chondroitin sulfate proteoglycan is DSD-1-PG/phosphacan,…
A new technique for real-time analysis of caspase-3 dependent neuronal cell death
Several markers are available to identify cells undergoing programmed cell death, but so far they are only applicable on fixed material. Therefore, no information on the kinetics of apoptosis can be obtained, although apoptosis is a dynamic cell process. Here, we describe a new technique that allows the real-time observation of the onset of apoptosis in primary neurons. Neurons are transfected with a plasmid that codes for a fluorescent protein localized in the soma. Upon activation of caspase-3, which represents the point-of-no-return in the apoptosis process, the fusion protein is cleaved and as a consequence translocates into the nucleus. The onset of apoptosis is thus visualized by tran…
Oxygen and glucose deprivation induces major dysfunction in the somatosensory cortex of the newborn rat
The mechanisms and functional consequences of ischemia-induced injury during perinatal development are poorly understood. Subplate neurons (SPn) play a central role in early cortical development and a pathophysiological impairment of these neurons may have long-term detrimental effects on cortical function. The acute and long-term consequences of combined oxygen and glucose deprivation (OGD) were investigated in SPn and compared with OGD-induced dysfunction of immature layer V pyramidal cortical neurons (PCn) in somatosensory cortical slices from postnatal day (P)0-4 rats. OGD for 50 min followed by a 10-24-h period of normal oxygenation and glucose supply in vitro or in culture led to pron…