Analysis of sequence-dependent interactions between transient calcium and transmitter stimuli in activating adenylyl cyclase in Aplysia: possible contribution to CS--US sequence requirement during conditioning.
An important recent insight in a number of neurobiological systems is that during learning, individual dually regulated proteins with associative properties function as critical sites of stimulus convergence. During conditioning in Aplysia, the Ca2+ /calmodulin-sensitive adenylyl cyclase (AC) in mechanosensory neurons serves as a molecular site of interaction between Ca2+ and serotonin [5-hydroxytryptamine (5-HT)]-two signals that represent the CS and US in these cells. Conditioning requires that the CS and US be paired within a narrow time window and in the appropriate sequence. AC shows an analogous sequence preference: It is more effectively activated when a pulse of Ca2+ precedes a pulse of 5-HT than when the 5-HT precedes Ca2+. One mechanism that contributes to this sequence preference is that Ca2+/calmodulin binding to AC accelerates the rate of AC activation by receptor-Gs. We have identified two additional properties of AC activation that would cause pairing with Ca2+ preceding 5-HT to be more effective than simultaneous pairing or pairing with the reciprocal sequence: (1) Activation of Aplysia AC by a Ca2+ pulse rose with a delay compared with activation by a 5-HT pulse. (2) A late pulse of Ca2+, which arrived after 5-HT, acted, via calmodulin, to accelerate the decay of AC activation by receptor-Gs. Together, these activation properties of AC may contribute to the CS-US sequence requirement of classical conditioning.
Abrams
T W
TW
Department of Pharmacology, University of Maryland School of Medicine, Baltimore 21201-1559, USA.
Yovell
Y
Y
Onyike
C U
CU
Cohen
J E
JE
Jarrard
H E
HE
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001048:Aplysia / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D003214:Conditioning, Classical / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
D018377:Neurotransmitter Agents; D005576:Colforsin; D012701:Serotonin; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D002118:Calcium