Cerebellar Purkinje neurons express voltage-gated Ca2+ channels that are located on their somata and dendrites. Previous reports, based on microelectrode recordings and fura-2 Ca2+ imaging, suggested that depolarization-mediated intracellular Ca2+ signaling is confined almost completely to the dendrites. We investigated the spatial distribution of depolarization-induced Ca2+ signals in Purkinje neurons by applying whole-cell patch-clamp recordings combined with fluorometric Ca2+ imaging to cerebellar slices. Under our recording conditions, depolarizing pulses produced the dendritic but also large somatic Ca2+ signals. By selective perfusion of the slice with a Ca(2+)-free EGTA-containing solution, we could isolate experimentally Ca2+ signals in somata and dendrites, respectively. Moreover, experiments performed on cerebellar slices from young rats (up to postnatal day 6), in which Purkinje neurons are almost completely devoid of dendrites, showed that Ca2+ currents produced by the activation of somatic Ca2+ channels are associated with Ca2+ transients similar to those seen in the somata of adult Purkinje neurons. Our results strongly indicate that the depolarization-induced somatic Ca2+ signals are caused by Ca2+ entry through voltage-gated channels located on the somatic membrane of Purkinje neurons.
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http://dx.doi.org/10.1016/0168-0102(95)00978-7 | DOI Listing |
Mol Biol Cell
January 2025
Department of Cell Biology, Emory University, 615 Michael St, Atlanta, GA, USA, 30322.
Rare inherited diseases caused by mutations in the copper transporters (CTR1) or induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation.
View Article and Find Full Text PDFSTAR Protoc
January 2025
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Initiative for Columbia Ataxia and Tremor, Columbia University, New York, NY 10032, USA. Electronic address:
As Purkinje cells of the cerebellum have a very fast firing rate, techniques with high temporal resolution are required to capture cerebellar physiology. Here, we present a protocol to record physiological signals in humans using cerebellar electroencephalography (cEEG). We describe steps for electrode placement and recording.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Neurology, University of Utah, Salt Lake City, UT 84112, USA.
Background: Christianson syndrome (CS) is an x-linked recessive neurodevelopmental and neurodegenerative condition characterized by severe intellectual disability, cerebellar degeneration, ataxia, and epilepsy. Mutations to the gene encoding NHE6 are responsible for CS, and we recently demonstrated that a mutation to the rat gene causes a similar phenotype in the spontaneous rat model, which exhibits cerebellar degeneration with motor dysfunction. In previous work, we used the PhP.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Paraneoplastic cerebellar degeneration (PCD) is an inflammatory autoimmune process caused by onconeural antibodies directed against cerebellar Purkinje cells. In most cases, prognosis is poor as disease progression leads to pancerebellar dysfunction and permanent neurological damage. Through this case report, we aim to highlight the clinical presentation, diagnostic process, and therapeutic implications associated with PCD secondary to SCLC.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Semaphorin 3A (Sema3A) is an axon guidance molecule, which is also abundant in the adult central nervous system (CNS), particularly in perineuronal nets (PNNs). PNNs are extracellular matrix structures that restrict plasticity. The cellular sources of Sema3A in PNNs are unknown.
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