Temporal asymmetry in activation of Aplysia adenylyl cyclase by calcium and transmitter may explain temporal requirements of conditioning.

Abstract

Cellular experiments have suggested that during dassical conditioning of the gill and siphon withdrawal reflex ofAplysia, adenylyl cyclase may serve as a molecular site of convergence for Ca2+ and serotonin (5-hydroxytryptamine; 5-HT), the cellular representations of the conditioned and unconditioned stimuli (CS and US). We explored the possible molecular basis of the behavioral requirement that the CS and US be paired within a narrow time window and in the appropriate order. To examine the temporal interactions of brief pulses of Ca2+ and 5-HT in stimulating Aplysia neural cyclase, we used a perfused-membrane cyclase assay. When briefpulses of Ca2W and 5-HT were paired, cyclase activation depended upon the sequence of the pulses: peak cyclase activation was greater when the Ca2+ pulse iediately preceded the 5-HT pulse. Eamination of the rising phase of 5-HT stimulation suggested that a Ca+ prepulse might accelerate the onset of activation by 5-HT, without affecting the final level of activation achieved with prolonged 5-HT exposure. The observed interactions between Ca2+ and transmitter in activating cyclase could contribute importantly to the temporal requirements of conditioning for CS-US pairing.

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

“…Pairing 5-HT and tetanus enhances sensory neuron excitability and action potential width, consistent with enhanced production of CAMP 1985; Yovell and Abrams, 1992). The above experiments indirectly support this conclusion by providing evidence against a contribution of the protein kinase C-mediated second process.…”

“…These findings suggested that Ca2+ influx during the paired activity enhances the first process of 5-HT facilitation, CAMP-dependent action potential broadening. Biochemical studies support this model, indicating that Ca2+ augments CAMP production by stimulating adenylate cyclase in concert with 5-HT (Ocorr et al, 1985;Eliot et al, 1989;Abrams et al, 1991;Yovell and Abrams, 1992). However, several questions remain concerning the molecular mechanism of the associative facilitation.…”

“…This enhancement is likely mediated by dual activation of adenylate cyclase by Cal+ and 5-HT (Eliot et al, 1989;Abrams et al, 199 1;Yovell and Abrams, 1992). Sensory neurons contain at least two different voltage-activated Ca*+ channels (Edmonds et al, 1990) raising the issue of the source of CaZ+ influx that contributes to pairing-specific facilitation.…”

Chemosensory-based contextual conditioning inHermissenda crassicornis

“…In general, activity-dependent models oflearning rely heavily on the temporal convergence (i.e., temporal contiguity) of short-lived CS-and US-induced intracellular events to account for synaptic plasticity. For instance, associative learning in both Aplysia and Hermissenda is said to occur when a CS-induced rise in intracellular Ca 2 + is potentiated by the temporal convergence of synaptic activity mediated by the US, such that Ca 2 +-sensitive enzymes are stimulated (Matzel & Rogers, 1993;Rogers et aI., 1994;Yovell & Abrams, 1992). These forms of"cellular learning" are temporally constrained in that the Ca 2 + signal induced by the CS dissipates rapidly owing to an inactivation of Ca 2 + currents and rapid intracellular buffering mechanisms.…”

Serotonin stimulation of cAMP-dependent plasticity in Aplysia sensory neurons is mediated by calmodulin-sensitive adenylyl cyclase

“…The coexpression of the Ca 2+ -inhibited AC-AplC and the CaMstimulated AC-AplA in the presynaptic sensory neurons suggests a possible role for Ca 2+ inhibition in enhancing the function of AC-AplA as a coincidence detector. Earlier biochemical and cellular studies on Aplysia neurons observed that activity and Ca 2 + alone are unable to effectively activate the cAMP cascade (38,51). Rather remarkably, cAMP-dependent kinase makes no contribution to posttetanic potentiation produced by trains of 40 action potentials at these SN-MN synapses (52), suggesting that even intense activity, which increases presynaptic Ca 2+ levels substantially, does not effectively increase cAMP levels.…”