Recent evidence suggests that altered postsynaptic activity induces homeostatic regulation of presynaptic transmitter release at vertebrate neuromuscular junction. The long-term goal of this study is to understand the in vivo mechanisms underlying the homeostatic regulation. A zebrafish preparation is developed in the lab wherein the spinal motor neuron and its target muscle cell can be simultaneously patch clamped in intact animal. Using this technique, synaptic transmission at the wild type neuromuscular junction will be first characterized. Secondly, the hypothesis that presynaptic release is regulated by postsynaptic activity will be tested following manipulations that alter the functional postsynaptic acetylcholine receptor density. Thirdly, available mutant fish lines with aberrant calcium signaling will be used to test for a role of calcium release from internal stores in initiating the retrograde signaling that leads to presynaptic compensation. Results from this study will contribute to our understanding of how synaptic transmission is maintained within a physiological range while allowing for activity-dependent modification, and understanding in etiology of related neural diseases. ? ?
| Wang, Meng; Wen, Hua; Brehm, Paul (2008) Function of neuromuscular synapses in the zebrafish choline-acetyltransferase mutant bajan. J Neurophysiol 100:1995-2004 |
