Sequence-dependent interactions between transient calcium and transmitter stimuli in activation of mammalian brain adenylyl cyclase

Allison H. Lin, Chiadi U. Onyike, Thomas W. Abrams

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)300-307
Number of pages8
JournalBrain research
Volume800
Issue number2
DOIs
StatePublished - Aug 3 1998
Externally publishedYes

Keywords

  • Adenylyl cyclase
  • Associative learning
  • Calcium
  • Calmodulin
  • Classical conditioning
  • Coincidence detector

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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