Axonal regeneration in the mammalian CNS is a property of immature neurons that is lost during development. Using organotypic culture of cerebellum, we have shown that in vitro Purkinje cells lose their regenerative capacity in parallel with the process of myelination. We have investigated whether myelination is involved in the age-dependent loss of regeneration of these neurons. By applying a ...

Cerebellar Purkinje cells contain intracellular membrane systems that are highly enriched in concanavalin A (Con A)-binding sites and which may be involved in axonal and dendritic transport. We have attempted to characterize these Con A-binding sites in fixed slices of cerebellum by their susceptibility to endoglycosidase H (Endo H) digestion. Tissue slices labeled with Con A-peroxidase without...

BACKGROUND DYT1 early-onset generalized dystonia is a neurological movement disorder characterized by involuntary muscle contractions. It is caused by a trinucleotide deletion of a GAG (ΔGAG) in the DYT1 (TOR1A) gene encoding torsinA; the mouse homolog of this gene is Dyt1 (Tor1a). Although structural and functional alterations in the cerebellum have been reported in DYT1 dystonia, neuronal mor...

Neurophysiological recordings in the cerebellar cortex of awake-behaving animals are revolutionizing the way we think about the role of Purkinje cells in sensori-motor calibration. Early theorists suggested that if a movement became miscalibrated, Purkinje cell output would be changed to adjust the motor command and restore good performance. The finding that Purkinje cell activity changed in ma...

In vitro, cerebellar Purkinje cells can intrinsically fire action potentials in a repeating trimodal or bimodal pattern. The trimodal pattern consists of tonic spiking, bursting, and quiescence. The bimodal pattern consists of tonic spiking and quiescence. It is unclear how these firing patterns are generated and what determines which firing pattern is selected. We have constructed a realistic ...

Zebrin II/aldolase C is a 36 kDa polypeptide expressed by Purkinje cells in the cerebellum of elasmobranchs, teleosts, birds, and mammals, and by octavolateralis pyramidal cells in developing teleosts. To better understand the evolution of these two systems we determined if zebrin II is expressed (1) in previously described primitive Purkinje cells, and (2) in octavolateralis pyramidal cells of...

The murine stem cell virus (MSCV) promoter exhibits activity in mouse hematopoietic cells and embryonic stem cells. We generated transgenic mice that expressed enhanced green fluorescent protein (GFP) under the control of the MSCV promoter. We obtained 12 transgenic founder mice through 2 independent experiments and found that the bodies of 9 of the founder neonates emitted different levels of ...

Purkinje cells are the principal neurons of the cerebellar cortex and have an extensive and elaborate dendritic tree. Chronic activation of type I metabotropic glutamate receptors inhibits Purkinje cell dendritic growth in organotypic cerebellar slice cultures. This effect is mediated by calcium influx through P/Q-type and T-type Ca(2+) channels. We have now studied the role of the plasma membr...

The Moonwalker (Mwk) mouse is a model of dominantly inherited cerebellar ataxia caused by a gain-of-function mutation in the transient receptor potential (TRP) channel TRPC3. Here, we report impairments in dendritic growth and synapse formation early on during Purkinje cell development in the Mwk cerebellum that are accompanied by alterations in calcium signaling. To elucidate the molecular eff...

PrP knockout mice with disruption of only the PrP-encoding region (Zürich I-type) remain healthy, whereas mice with deletions extending upstream of the PrP-encoding exon (Nagasaki-type) suffer Purkinje cell loss and ataxia, associated with ectopic expression of Doppel in brain, particularly in Purkinje cells. The phenotype is abrogated by co-expression of full-length PrP. Doppel is 25% similar ...