ACTIVITY-DEPENDENT ENHANCEMENT OF PRESYNAPTIC FACILITATION PROVIDES ACELLULAR MECHANISM FOR THE TEMPORAL SPECIFICITY OF CLASSICAL-CONDITIONING IN APLYSIA

A hallmark of many forms of classical conditioning is a precise tempor al specificity: Learning is optimal when the conditioned stimulus (CS) slightly precedes the unconditioned stimulus (US), but the learning i s degraded at longer or backward intervals, consistent with the notion that conditioning involves learning about predictive relationships in the environment, To further examine the cellular mechanisms contribut ing to the temporal specificity of classical conditioning of the sipho n-withdrawal response in Aplysia, we paired action potential activity in siphon sensory neurons (the neural CS) with tail nerve shock (the U S) at three critical time points. We found that CS-US pairings at shor t (0.5 sec) forward intervals produced greater synaptic facilitation a t sensorimotor connections than did either 0.5-sec backward pairings o r longer (5 sec) forward pairings, as reflected in a differential incr ease in both the amplitude and rate of rise of the synaptic potential. Ln the same preparations, forward pairings also differentially reduce d the sensory neuron afterhyperpolarization relative to backward pairi ngs, suggesting that changes in synaptic efficacy were accompanied by temporally specific changes in ionic currents in the sensory neurons. Additional experiments demonstrated that short forward pairings of sen sory cell activity and restricted applications of the neuromodulatory transmitter serotonin (normally released by the US) differentially enh anced action potential broadening in siphon sensory neurons, relative to backward pairings. Taken together, these results suggest that tempo rally specific synaptic enhancement engages both spike-width-dependent and spike-width-independent facilitatory processes and that activity- dependent enhancement of presynaptic facilitation may contribute to bo th the CS-US sequence and proximity requirements of conditioning.