Prolongation of Evoked and Spontaneous Synaptic Currents at the Neuromuscular Junction after Activity Blockade Is Caused by the Upregulation of Fetal Acetylcholine Receptors

Wang, Xueyong; Engisch, Kathrin L.; Teichert, Russell W.; Olivera, Baldomero M.; Pinter, Martin J.; Rich, Mark M.

doi:10.1523/jneurosci.2493-06.2006

Cited by 18 publications

(19 citation statements)

References 26 publications

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“…We find that the gross morphology of the NMJ is unchanged under such conditions. There is no alteration in the level of receptor expression at silenced junctions, in agreement with observations following short term pharmacological inhibition of action potentials 26,27 . We also considered the possibility that active axons might invade or take over inactive NMJs, similar to the manner in which denervated NMJs can be innervated by sprouting axons from intact neighboring junctions 28 .…”

Section: Discussionsupporting

confidence: 90%

Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice

et al. 2008

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To facilitate functional analysis of neuronal connectivity in a mammalian nervous system tightly packed with billions of cells, we developed a new technique that allows inducible genetic manipulations within fluorescently labeled single neurons in mice. We term this technique SLICK for Single-neuron Labeling with Inducible Cre-mediated Knockout. SLICK is achieved by coexpressing a drug-inducible form of cre recombinase and a fluorescent protein within the same small subsets of neurons. Thus, SLICK combines the powerful cre recombinase system for conditional genetic manipulation and the fluorescent labeling of single neurons for imaging. We demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we apply SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals. More broadly, these studies demonstrate a cre-LoxP compatible system for dissecting gene functions in single identifiable neurons.

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Section: Discussionsupporting

confidence: 90%

Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice

et al. 2008

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“…If skeletal muscle produced the ␥-subunit-containing embryonic form of the AChR during diabetes, then this would contribute to prolonged mEPCs (59,73). We tested for this possibility in two ways.…”

Section: Resultsmentioning

confidence: 99%

“…First, diabetes might induce expression of embryonic AChRs that have a longer open time that accounts for the prolonged decay of mEPCs at developing and regenerating NMJs (6,20,51,59,73). In normally active mature muscle, expression of the adult AChR isoform containing the ε-subunit is dominant, and there are very low levels of The reduced staining intensity and size for EDL of diabetic animals suggest decreased AChE activity.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholinesterase deficiency contributes to neuromuscular junction dysfunction in type 1 diabetic neuropathy

Garcia¹,

Potian²,

Hognason³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Diabetic neuropathy is associated with functional and morphological changes of the neuromuscular junction (NMJ) associated with muscle weakness. This study examines the effect of type 1 diabetes on NMJ function. Swiss Webster mice were made diabetic with three interdaily ip injections of streptozotocin (STZ). Mice were severely hyperglycemic within 7 days after the STZ treatment began. Whereas performance of mice on a rotating rod remained normal, the twitch tension response of the isolated extensor digitorum longus to nerve stimulation was reduced significantly at 4 wk after the onset of STZ-induced hyperglycemia. This mechanical alteration was associated with increased amplitude and prolonged duration of miniature end-plate currents (mEPCs). Prolongation of mEPCs was not due to expression of the embryonic acetylcholine receptor but to reduced muscle expression of acetylcholine esterase (AChE). Greater sensitivity of mEPC decay time to the selective butyrylcholinesterase (BChE) inhibitor PEC suggests that muscle attempts to compensate for reduced AChE levels by increasing expression of BChE. These alterations of AChE are attributed to STZ-induced hyperglycemia since similar mEPC prolongation and reduced AChE expression were found for db/db mice. The reduction of muscle end-plate AChE activity early during the onset of STZ-induced hyperglycemia may contribute to endplate pathology and subsequent muscle weakness during diabetes.

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“…For lowering the probability of release for ANOVA, recordings were done in 1 mM Ca 2ϩ solution in which the Mg 2ϩ concentration was kept at 0.7 mM. Endplate recordings were performed as previously described (Wang et al 2004(Wang et al , 2006(Wang et al , 2010. Briefly, the tibialis anterior muscle was pinned in a dish and stained with 10 M 4-(4-diethylaminostyryl)-N-methylpyridinium iodide (4-Di-2ASP; Invitrogen, Carlsbad, CA).…”

Section: Electrophysiologic Recordingmentioning

confidence: 99%

Activity-Dependent Regulation of the Binomial Parameters p and n at the Mouse Neuromuscular Junction In Vivo

Wang

Engisch

et al. 2010

Journal of Neurophysiology

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Block of neurotransmission at the mammalian neuromuscular junction triggers an increase in the number of vesicles released (quantal content). The increase occurs whether nerve and muscle activity are both blocked by placement of a tetrodotoxin (TTX) containing cuff on the nerve or whether muscle activity is selectively blocked by injection of α-bungarotoxin (BTX). We used ANOVA to examine whether the mechanism underlying the increase in quantal content differed between the two types of activity blockade. We found that TTX-induced blockade increased the probability of release (p), whereas BTX-induced blockade increased the number of releasable vesicles (n). The lack of increase in p when postsynaptic activity was blocked with BTX suggests that block of presynaptic activity triggers the increase. To determine whether n is regulated by mismatch of pre- and postsynaptic activity introduced by BTX injection we combined BTX and TTX and still found an increase in n. We conclude that block of acetylcholine binding to acetylcholine receptors during spontaneous release triggers the increase in n.

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Prolongation of Evoked and Spontaneous Synaptic Currents at the Neuromuscular Junction after Activity Blockade Is Caused by the Upregulation of Fetal Acetylcholine Receptors

Cited by 18 publications

References 26 publications

Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice

Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice

Acetylcholinesterase deficiency contributes to neuromuscular junction dysfunction in type 1 diabetic neuropathy

Activity-Dependent Regulation of the Binomial Parameters p and n at the Mouse Neuromuscular Junction In Vivo

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