Niemann-Pick type C disease is a rare and ultimately fatal lysosomal storage disorder with variable neurologic symptoms. The disease-causing mutations concern NPC1 or NPC2, whose dysfunction entails accumulation of cholesterol in the endosomal-lysosomal system and the selective death of specific neurons, namely cerebellar Purkinje cells. Here, we investigated whether neurodegeneration is preced...

The electrophysiological properties of subendocardial Purkinje fibers surviving in myocardial infarcts were studied with intracellular microelectrodes in isolated superfused preparations and correlated with subsequent light and electron microscopic studies. Transmembrane action potentials could always be recorded from one or two cell layers of subendocardial Purkinje fibers in infarcted regions...

Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. The proper connectivity of zones is critical for motor coordination and motor learning, and in several neurological diseases cerebellar circuits degenerate in zonal patterns. Despite recent advances in understanding zone function, we still have a limited understanding of how zones are formed. Here,...

Secretin, a peptide hormone of the gastrointestinal system, has been implicated in the etiology of autism. Our laboratory previously demonstrated the expression of secretin and its receptors in specific central neurons, and found for the first time that secretin is neuroactive in the cerebellum. We showed that bath application of secretin facilitated the release of GABA from terminals of basket...

Secretin, a peptide hormone of the gastrointestinal system, has been implicated in the etiology of autism. Our laboratory previously demonstrated the expression of secretin and its receptors in specific central neurons, and found for the first time that secretin is neuroactive in the cerebellum. We showed that bath application of secretin facilitated the release of GABA from terminals of basket...

To investigate whether the c-fms proto-oncogene plays a role in the CNS, we examined its expression in mouse brain. We found that c-fms-positive Purkinje cells first appeared in caudal cerebellum at postnatal day 0 (P0) arranged in a parasagittal manner, and most Purkinje cells gradually became positive by P6. This differential expression was not seen from P7 to adulthood, and the parasagittal ...

Calbindin is a fast Ca2+-binding protein expressed by Purkinje cells and involved in their firing regulation. Its deletion produced approximately 160-Hz oscillation sustained by synchronous, rhythmic Purkinje cells in the cerebellar cortex of mice. Parvalbumin is a slow-onset Ca2+-binding protein expressed in Purkinje cells and interneurons. In order to assess its function in Purkinje cell firi...

Among integrative neurons displaying long-term synaptic plasticity, adult Purkinje cells seemed to be an exception by lacking functional NMDA receptors (NMDA-Rs). Although numerous anatomical studies have shown both NR1 and NR2 NMDA-R subunits in adult Purkinje cells, patch-clamp studies failed to detect any NMDA currents. Using more recent pharmacological and immunodetection tools, we demonstr...

Reciprocal activity between populations of neurons has been widely observed in the brain and is essential for neuronal computation. The different mechanisms by which reciprocal neuronal activity is generated remain to be established. A common motif in neuronal circuits is the presence of afferents that provide excitation to one set of principal neurons and, via interneurons, inhibition to a sec...

The mammalian GABAJbenzodiazepine (GABAJBZ) receptor is comprised of several subunit isoforms: cq6, f3.3, Y,.~ and 6. In the present studies, the expression of (Y,, p2, and y2 subunit mFiNAs was examined in cerebellar Purkinje cells and deep cerebellar neurons of staggerer mutant mice during postnatal development. In control animals, the three subunit mRNAs were present at high density in Purki...