Cerebral cortex
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Comparative Study
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. ⋯ Furthermore, this effect involved phosphorylation of cAMP response element-binding protein and activation of the tropomyosin-related kinase (Trk) receptors. Inhibition of electrical synapses and blockade of ionotropic gamma-aminobutyric acid receptors induced specific changes in spontaneous electrical activity patterns, which caused an increase in caspase-3-dependent cell death. Our results demonstrate that synchronized spontaneous network bursts activating ionotropic glutamate receptors promote neuronal survival in the neonatal mouse cerebral cortex.
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Comparative Study
Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression.
Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. ⋯ At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.