2000 West Coast Worm Meeting abstract 27
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361 LSA, Univ. of Cal., Berkeley, CA 94720
The ability of neurons to alter their synaptic function underlies our ability to control behavior. We are interested in understanding how neurotransmitters like serotonin (5-HT) cause changes in neuron and synapse function to effect behavioral changes. In C. elegans, 5-HT modulates the rate of locomotion. Recent analysis has shown that 5-HT acts presynaptically on motor neurons through a G-protein Gao subunit, GOA-1, to reduce acetylcholine (ACh) release at body wall neuromuscular junctions (NMJs) [1]. Using a recently developed dissection technique and whole cell voltage clamp recordings [2], we have recorded the effects of 5-HT on adult body wall NMJ physiology.
We have recorded from body wall muscle both miniature excitatory post-synaptic currents (mEPSCs) and muscle responses to ACh application in the presence of 5-HT. We see two effects of 5-HT: a reduction in EPSC frequency and a reduction in ACh-activated current amplitude. The amplitude of ACh-activated current is reduced by 40% in the presence of 5-HT. Previous physiological analysis by Richmond and Jorgensen has shown there to be two classes of ACh receptors at the body wall NMJ; one ACh receptor class is sensitive to the cholinergic agonist levamisole and one receptor is insensitive [2]. Recordings of levamisole-activated current show that 5-HT reduces this current up to 90%. These data suggest that the levamisole activated ACh receptors may be specifically modulated by 5-HT. To resolve the contribution of post-synaptic modulation by 5-HT to presynaptic changes in mEPSC frequency and to further understand the mechanism of the post-synaptic response, we have recorded from mutants that might eliminate the post-synaptic ACh receptor modulation. Since 5-HT's downstream effects are mediated by G-protein coupled pathways, we have tested a number of candidate signal transduction mutants expressed in muscle for defects in ACh receptor modulation. We have tested the G-protein Ga subunit mutants, gpa-14 and gpa-7, and an adenylate cyclase, acy-1, and all are normal for ACh receptor modulation by 5-HT. Future physiologic and genetic experiments will help further our understanding of 5-HT's modulation of synaptic function and behavior.
1. Nurrish et al., Neuron 24: 231-242 1999.
2. Richmond and Jorgensen, Nat Neurosci 2: 791-797 1999.