Sequence-dependent interactions between transient calcium and transmitter stimuli in activation of mammalian brain adenylyl cyclase.
Recent evidence implicates Ca2+/CaM-sensitive adenylyl cyclase (AC) as a molecular coincidence detector for temporally paired stimuli during associative learning. During conditioning in Aplysia, AC is optimally activated when Ca2+ influx, the cellular signal for the conditioned stimulus (CS), precedes binding of modulatory transmitter, the cellular signal for the unconditioned stimulus (US). This sequence preference of the AC for Ca2+-before-transmitter, parallels the CS-preceding-US pairing requirement of classical conditioning. In this study, we have examined the response of AC from rat cerebellum to brief exposures to Ca2+ and to transmitter in a perfused membrane assay. We observed modest synergism between Ca2+ and transmitter in activating AC. Activation was more effective when a Ca2+ stimulus immediately preceded a transmitter stimulus than when the two stimuli were delivered in the reverse order. Thus, rat cerebellar AC displayed a sequence preference for optimal activation by paired stimuli similar to that observed in Aplysia; this sequence dependence could contribute to the CS-US sequence requirement observed in most mammalian classical conditioning paradigms.
Department of Pharmacology, University of Maryland School of Medicine, BRB 4-002, 655 West Baltimore Street, Baltimore, MD 21201-1559, USA.
A H
AH
Lin
C U
CU
Onyike
T W
TW
Abrams
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001245:Association Learning / Q000502:physiology; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D003214:Conditioning, Classical / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D002147:Calmodulin; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002118:Calcium; D004298:Dopamine