Specific plasticity loci and their synergism mediate operant conditioning

Abstract

Despite numerous studies examining the mechanisms of operant conditioning (OC), the diversity of plasticity loci and their synergism have not been examined sufficiently. In the well-characterized feeding neural circuit of Aplysia, appetitive OC increases neuronal excitability and electrical coupling among several neurons. Here we found OC decreased the intrinsic excitability of B4 and the strength of its inhibitory connection to a key decision-making neuron, B51. The OC-induced changes were specific without affecting the B4-to-B8 inhibitory connection or excitability of another neuron critical for feeding behavior, B8. A conductance-based circuit model indicated certain sites of plasticity mediated the OC phenotype more effectively and that plasticity loci acted synergistically. This synergy was specific in that only certain combinations of loci synergistically enhanced feeding. Taken together, these results suggest modifications of diverse loci work synergistically to mediate OC. Significance StatementThe diversity and synergism of plasticity loci mediating operant conditioning (OC) is poorly understood. Here we found that OC decreased the intrinsic excitability of a critical neuron mediating Aplysia feeding behavior and specifically reduced the strength of one of its inhibitory connections to a key decision-making neuron. A conductance-based computational model indicated that the known plasticity loci showed a surprising level of synergism to mediate the behavioral changes associated with OC. These results highlight the importance of understanding the diversity, specificity and synergy among different types of plasticity that encode memory. Also, because OC in Aplysia is mediated by dopamine (DA), the present study provides insights into specific and synergistic mechanisms of DA-mediated reinforcement of behaviors.