Neuromuscular activity blockade induced by muscimol and d-tubocurarine differentially affects the survival of embryonic chick motoneurons

To understand better how spontaneous motoneuron activity and intramuscular nerve branching influence motoneuron survival, we chronically treated chick en embryos in ovo with either d-tubocurarine (dTC) or muscimol during the n aturally occurring cell death period, assessing their effects on activity b y in ovo motility measurement and muscle nerve recordings from isolated spi nal cord preparations. Because muscimol, a GABA(A) agonist, blocked both sp ontaneous motoneuron bursting and that elicited by descending input but did not rescue motoneurons, we conclude that spontaneous bursting activity is not required for the process of normal motoneuron cell death. dTC, which re scues motoneurons and blocks neuromuscular transmission, blocked neither sp ontaneous nor descending input-elicited bursting and early in the cell deat h period actually increased burst amplitude. These changes in motoneuron ac tivation could alter the uptake of trophic molecules or gene transcription via altered patterns of [Ca2+](i), which in turn could affect motoneuron su rvival directly or indirectly by altering intramuscular nerve branching. A good correlation was found between nerve branching and motoneuron survival under various experimental conditions: (1) dTC, but not muscimol, greatly i ncreased branching; (2) the removal of PSA from NCAM partially reversed the effects of dTC on both branching and survival, indicating that branching i s a critical variable influencing motoneuron survival; (3) muscimol, applie d with dTC, prevented the effect of dTC on survival and motoneuron bursting and, to a large extent, its effect on branching. However, the central effe cts of dTC also appear to be important, because muscimol, which prevented m otoneuron activity in the presence of dTC, also prevented the dTC-induced r escue of motoneurons.