Combined effects of intrinsic facilitation and modulatory inhibition of identified interneurons in the siphon withdrawal circuitry of Aplysia

Synaptic plasticity can be induced through mechanisms intrinsic to a synaps e or through extrinsic modulatory mechanisms. In this study, we investigate d the relationship between these two forms of plasticity at the excitatory synapse between L29 interneurons and siphon motor neurons (MNs) in Aplysia. Using isolated ganglia, we confirmed that the L29-MN synapses exhibit a fo rm of intrinsic facilitation: post-tetanic potentiation (PTP). We also foun d that L29-MN synapses are modulated by exogenous application of 5-HT: they are depressed after 5-HT exposure. We next investigated the functional rel ationship between an intrinsic facilitatory process (PTP) and extrinsic inh ibitory modulation (5-HT-induced depression). First, we found that applicat ion of 5-HT just before L29 activation results in a reduction of PTP. Secon d, using semi-intact preparations, we found that tail shock (TS) mimics the effect of 5-HT by both depressing L29 synaptic transmission and by reducin g L29 PTP. Third, we observed a significant correlation between L29 activit y during TS and subsequent synaptic change: low-responding L29s showed syna ptic depression after TS, whereas high-responding L29s showed synaptic faci litation. Finally, we found that we could directly manipulate the sign and magnitude of TS-induced synaptic plasticity by controlling L29 activity dur ing TS. Collectively, our results show that the L29-MN synapses exhibit int rinsic facilitation and extrinsic modulation and that the sign and magnitud e of L29-MN plasticity induced by TS is governed by the combined effects of these two processes. This circuit architecture, which combines network inh ibition with cell-specific facilitation, can enhance the signal value of a specific stimulus within a neural network.