The Journal of neuroscience : the official journal of the Society for Neuroscience
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Purkinje cells have two action potentials: Climbing fiber responses (CFRs) and simple spikes (SSs). CFRs reflect the discharge of a single climbing fiber at multiple synaptic sites on the proximal dendrite of the Purkinje cell. SSs reflect the summed action of a subset of parallel fiber synapses on Purkinje cell dendritic spines. ⋯ Vestibular climbing fibers not only evoke low-frequency CFRs, but also indirectly modulate higher-frequency SSs. This modulation must be attributed to cerebellar interneurons. Golgi cell inhibition of granule cells may provide the interneuronal mechanism for CFR-induced SS modulation.
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The dorsal side-up body orientation in quadrupeds is maintained by a postural system that is driven by sensory feedback signals. The spinal cord, brainstem, and cerebellum play essential roles in postural control, whereas the role of the forebrain is unclear. In the present study we investigated whether the motor cortex is involved in maintenance of the dorsal side-up body orientation. ⋯ This finding suggests that the motor cortex is involved in postural control. In contrast to CF5 neurons, other classes of efferent neurons (CCI, CCC, CF6) were much less active during postural corrections. This suggests that corticocortical interactions, both within a hemisphere (mediated by CCIs) and between hemispheres (mediated by CCCs), as well as corticothalamic interactions via CF6 neurons are not essential for motor coordination during postural corrections.
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Auditory afferents terminating as "large myelinated club endings" on goldfish Mauthner cells are identifiable "mixed" (electrical and chemical) synaptic terminals that offer the unique opportunity to correlate physiological properties with biochemical composition and specific ultrastructural features of individual synapses. By combining confocal microscopy and freeze-fracture replica immunogold labeling (FRIL), we demonstrate that gap junctions at these synapses contain connexin35 (Cx35). This connexin is the fish ortholog of the neuron-specific human and mouse connexin36 that is reported to be widely distributed in mammalian brain and to be responsible for electrical coupling between many types of neurons. ⋯ We show evidence by confocal microscopy for the presence of the NR1 subunit of the NMDA glutamate receptor subtype, proposed to be a key regulatory element, at these large endings. Furthermore, we also show evidence by FRIL double-immunogold labeling that the NR1 subunit of the NMDA glutamate receptor is present at postsynaptic densities closely associated with gap junction plaques containing Cx35 at mixed synapses across the goldfish hindbrain. Given the widespread distribution of electrical synapses and glutamate receptors, our results suggest that the plastic properties observed at these identifiable junctions may apply to other electrical synapses, including those in mammalian brain.
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Alzheimer's disease (AD) is characterized by a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. Nonsteroidal anti-inflammatory drug (NSAID) treatment reduces AD risk, slows disease progression, and reduces microglial activation; however, the basis of these effects is unknown. We report that treatment of 11-month-old Tg2576 mice overexpressing human amyloid precursor protein (APP) with the NSAID ibuprofen for 16 weeks resulted in the dramatic and selective reduction of SDS-soluble beta-amyloid (Abeta)42, whereas it had smaller effects on SDS-soluble Abeta40 levels. ⋯ Ibuprofen treatment resulted in a significant reduction in microglial activation in the Tg2576 mice, as measured by CD45 and CD11b expression. NSAIDs activate the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma); however, a potent agonist of this receptor, pioglitazone, only modestly reduced SDS-soluble Abeta levels and did not affect amyloid plaque burden or microglia activation, indicating that PPARgamma activation is not involved in the Abeta lowering effect of NSAIDs. These data show that chronic NSAID treatment can reduce brain Abeta levels, amyloid plaque burden, and microglial activation in an animal model of Alzheimer's disease.
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Dendritic filopodia are long and thin protrusions that occur predominantly during early development of the mammalian CNS. The function of dendritic filopodia is unknown, but they could serve to form early synapses, to generate spines, or to regulate dendritic branching and growth. We used two-photon imaging to characterize the motile behavior of dendritic protrusions during early postnatal development (P2-P12) in pyramidal neurons from acute slices of mouse neocortex. ⋯ Moreover, blocking ionotropic glutamate receptors resulted in an approximately 35% decrease in the density and turnover of shaft filopodia, whereas focal glutamate application led to a 75% increase in the length of shaft filopodia, but neither manipulation affected growth cone filopodia. Our results support the existence of two populations of filopodia, in growth cones and shafts, which are differentially regulated by neuronal activity. We propose that filopodia in dendritic growth cones are involved in dendritic growth and branching in an activity-independent manner, whereas shaft filopodia are responsible for activity-dependent synaptogenesis and, in some cases, may become dendritic spines.