Synaptic Plasticity in the Cerebral Ganglion of Aplysia

Abstract

The A-B neuron synapses in the cerebral ganglion of Aplysia exhibit two prominent forms of activity-dependent plasticity. Stimulating individual presynaptic A neurons at low frequencies (0.002-5 Hz) causes synaptic depression of EPSPs and EPSCs in postsynaptic B neurons, while tetanizing A neurons with 4,500 ms trains of 35 ms pulses at 20 Hz evokes a long-lasting (~25 min) increase in EPSP amplitudes. Due to its slow kinetics, we have called this latter plasticity slow developing potentiation (SDP). Both depression and SDP are neuron-specific. Several lines of evidence support the hypothesis that SDP has a presynaptic locus. SDP can be induced while voltage clamping the postsynaptic neuron. There are no changes in either input resistance or the steady-state I-V curve of B neurons during SDP. SDP does not require depolarization and spiking by the postsynaptic neuron. Pairing pre- and postsynaptic tetanization fails to increase SDP. Additionally, the reversal potential of the control and potentiated EPSCs are essentially the same (+ 11-12 mV). In contrast, there is a significant reduction in total outward current in the presynaptic A neurons following the tetanization. However, SDP does not appear to be due to the inactivation of a steady-state K+ current. SDP may be in part mediated by PKC. PKC activators enhance SDP, while injecting the peptide inhibitor PKC19-36 blocks it. Both Ca2+ entry, antagonized by L-channel blockers and ryanodine-sensitive release of Ca2+ from internal stores appear to contribute to SDP. Using quantal analysis, three independent measures indicate that SDP is due to increased quantal content. All these changes are consistent with an SDP requiring an increase in intracellular Ca2+, leading to increased transmitter release and a primary, if not exclusive, presynaptic locus for the observed synaptic plasticity.