Quantitative fluorescence imaging was used to study the regulation of acetylcholine receptor (AChR) number and density at neuromuscular junctions in living adult mice. At fully functional synapses, AChRs have a half-life of about 14 days. However, 2 hours after neurotransmission was blocked, the half-life of the AChRs was now less than a day; the rate was 25 times faster than before. Most of the lost receptors were not quickly replaced. Direct muscle stimulation or restoration of synaptic transmission inhibited this process. AChRs that were removed from nonfunctional synapses resided for hours in the perijunctional membrane before being locally internalized. Dispersed AChRs could also reaggregate at the junction once neurotransmission was restored. The rapid and reversible alterations in AChR density at the neuromuscular junction in vivo parallel changes thought to occur in the central nervous system at synapses undergoing potentiation and depression.
Radial glia are transiently present in the developing cerebral cortex, where they are thought to guide the migration of neurons from the proliferative zone to the forming cortical plate. To provide a framework for experimental studies of radial glia, we have defined morphological and immunocytochemical criteria to identify them in primary cultures of cortical cells obtained at embryonic day 13 in the mouse. Cortical radial glia in culture for 1-2 d resemble radial glia in vivo: they have a long, thin, unbranched process extending from one or both ends of the elongated cell body and are labeled with the monoclonal antibody RC1 but not with antibodies to glial fibrillary acidic protein (abGFAP). We tested the specificity of RC1 by double-labeling with a panel of cell-type specific antibodies, and found that it labels radial glia, astrocytes, and fibroblast-like cells, but not neurons. Fibroblasts are easily distinguished from glia by morphology and by labeling with antibodies to fibronectin. To test the hypothesis that radial glia become astrocytes when their developmental role is complete, we examined their morphological and immunocytochemical development in culture. After 3-4 d in vitro radial glia develop several branched processes; in this transitional stage they are labeled by both RC1 and abGFAP. Many radial glia lose RC1 immunoreactivity as they become increasingly branched and immunoreactive to abGFAP. In areas of the cultures that have few neurons and in cultures depleted of neurons by washing, flat, nonprocess-bearing glia predominate. These cells do not lose immunoreactivity to RC1 during the 9-d period of observation even though they acquire GFAP.(ABSTRACT TRUNCATED AT 250 WORDS)
IMPORTANCE Although almost equal numbers of male and female medical students enter into ophthalmology residency programs, whether they have similar surgical experiences during training is unclear.OBJECTIVE To determine differences for cataract surgery and total procedural volume between male and female residents during ophthalmology residency.
Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role, remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors (PRs) fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx−/− mice become rhythmically hyperactive around the time of eye-opening; as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. While hyperactivity in Crx−/− mice persists, synapse numbers do not increase beyond four weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell type-specific layers in the dorsolateral geniculate nucleus (dLGN).
TSCP and ECP are safe, effective, and comparable treatments for pediatric glaucomas. The results suggest that TSCP and ECP may be considered first-line therapy to achieve control of IOP in all forms of pediatric glaucoma. [J Pediatr Ophthalmol Strabismus 2014;51(2):120-127.].
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