Unique ionotropic receptors for D-aspartate are a target for serotonin-induced synaptic plasticity in Aplysia californica

The non-l-glutamate (l-Glu) receptor component of d-aspartate (d-Asp) currents in Aplysia californica buccal S cluster (BSC) neurons was studied with whole cell voltage clamp to differentiate it from receptors activated by other well-known agonists of the Aplysia nervous system and investigate modulatory mechanisms of d-Asp currents associated with synaptic plasticity. Acetylcholine (ACh) and serotonin (5-HT) activated whole cell excitatory currents with similar current voltage relationships to d-Asp. These currents, however, were pharmacologically distinct from d-Asp. ACh currents were blocked by hexamethonium (C6) and tubocurarine (d-TC), while d-Asp currents were unaffected. 5-HT currents were blocked by granisetron and methysergide (MES), while d-Asp currents were unaffected. Conversely, while (2S,3R)-1-(Phenanthren- 2-carbonyl)piperazine-2,3-dicarboxylic acid(PPDA) blocked d-Asp currents, it had no effect on ACh or 5-HT currents. Comparison of the charge area described by currents induced by ACh or 5-HT separately from, or with, d-Asp suggests activation of distinct receptors by all 3 agonists. Charge area comparisons with l-Glu, however, suggested some overlap between l-Glu and d-Asp receptors. Ten minute exposure to 5-HT induced facilitation of d-Asp-evoked responses in BSC neurons. This effect was mimicked by phorbol ester, suggesting that protein kinase C (PKC) was involved.