Reversal of synaptic depression by serotonin at Aplysia sensory neuron synapses involves activation of adenylyl cyclase.
Facilitation of the monosynaptic connection between siphon sensory neurons and gill and siphon motor neuron contributes to sensitization and dishabituation of the gill and siphon withdrawal reflex in Aplysia. The facilitatory transmitter serotonin (5-HT) initiates two mechanisms that act in parallel to increase transmitter release from siphon sensory neurons. 5-HT acts, at least partly through cAMP, to broaden the presynaptic action potential. 5-HT also initiates a second process that facilitates depressed sensory neuron synapses by a mechanism independent of changes in action potential duration. Recent experiments indicated that either of two protein kinases, cAMP-dependent protein kinase A and protein kinase C, are capable of effectively activating this second facilitatory mechanism, restoring synaptic transmission in depressed synapses. We have used the adenylyl cyclase inhibitor SQ 22,536 [9-(tetrahydro-2-furyl)adenine or THFA] to explore the contribution of cAMP to the reversal of synaptic depression. THFA effectively inhibited both adenylyl cyclase activity in vitro and known cyclase-mediated effects in intact sensory neurons. THFA also completely blocked facilitation of depressed synapses by 5-HT. These results suggest that adenylyl cyclase plays a critical role in the reversal of synaptic depression that contributes to dishabituation in this system.
Goldsmith
B A
BA
Department of Biology, University of Pennsylvania, Philadelphia 19104.
Abrams
T W
TW
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D004789:Enzyme Activation; D005071:Evoked Potentials / Q000187:drug effects; D005724:Ganglia / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D000262:Adenylyl Cyclases; D000225:Adenine