Early postnatal developmental changes in N-methyl-d-aspartate (NMDA) receptor (NR) subunits regulate cerebellar granule cell maturation and potentially Purkinje cell development. We therefore investigated Purkinje cell morphology in slice cultures from mice with genetic subunit exchange from NR2C to NR2B (NR2C-2B). NR2C-2B Purkinje cells after 12 days in vitro showed a significantly impaired de...

Cerebellar Purkinje cells elaborate one of the most complex dendritic arbors among neurons to integrate the numerous signals they receive from the cerebellum circuitry. Their dendritic differentiation undergoes successive, tightly regulated phases of development involving both regressive and growth events. Although many players regulating the late phases of Purkinje cell dendritogenesis have be...

Neurotrophins cooperate with neural activity to modulate CNS neuronal survival and dendritic differentiation. In a previous study, we demonstrated that a critical balance of neurotrophin and neural activity is required for Purkinje cell survival in cocultures of purified granule and Purkinje cells (Morrison and Mason, 1998). Here we investigate whether TrkB signaling regulates dendrite and spin...

The electrophysiological characteristics of subendocardial Purkinje and myocardial cells were studied during acute (within 30 minutes) and chronic (after 10 days) phases of myocardial infarction. Endocardial Purkinje and myocardial electrograms were recorded in vivo with bipolar electrodes before and after occlusion of the anterior descending coronary artery. Also, intracellular and extracellul...

The maturation of cerebellar Purkinje cells of normal and nervous (nr/nr) mutant mice has been studied by light and electron microscopy. In the mutant, 90% of Purkinje cells selectively degenerate between postnatal days 23 and 50. Losses are greater in lateral than medial regions. Other cerebellar neurons appear normal. The first morphological abnormality recognized is the presence of rounded m...

The Scn8a gene encodes the voltage-gated Na channel α subunit NaV1.6, which is widely expressed throughout the nervous system. Global null mutations that eliminate Scn8a in all cells result in severe motor dysfunction and premature death, precluding analysis of the physiological role of NaV1.6 in different neuronal types. To test the effect of cerebellar NaV1.6 on motor coordination in mice, we...

Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinj...

Ibogaine, an indole alkaloid that causes hallucinations, tremor, and ataxia, produces cerebellar neurotoxicity in rats, manifested by degeneration of Purkinje cells aligned in narrow parasagittal bands that are coextensive with activated glial cells. Harmaline, a closely related alkaloid that excites inferior olivary neurons, causes the same pattern of Purkinje cell degeneration, providing a cl...

Electrophysiological mechanisms which underlie the ectopic ventricular beats occurring 1 day after occlusion of the anterior descending coronary artery of dogs were explored. In intact dogs, bipolar electrograms were recorded in the infarcted and normal zones. Both Purkinje and ordinary myocardial potentials were recorded from the endocardial surface of the normal zone, but only Purkinje potent...

The human superoxide dismutase 1 (SOD1) gene is responsible for neutralizing supercharged oxygen radicals within the cell. Mutation in SOD1 gene causes amyotrophic lateral sclerosis (ALS). Recent studies have shown involvement of the cerebellum in ALS, although the cerebellar contribution in SOD1 transgenic mice remains unclear. Using immunohistopathology, we investigated the Purkinje cell phen...