Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School at the, University of Texas Health Science Center, Houston, Texas 77030.
Center for Nursing Research, Education and Practice, Houston Methodist Academic Institute, Houston, Texas 77030.
J Neurosci. 2022 Feb 16;42(7):1211-1223. doi: 10.1523/JNEUROSCI.1722-21.2021. Epub 2022 Jan 6.
Despite numerous studies examining the mechanisms of operant conditioning (OC), the diversity of OC plasticity loci and their synergism have not been examined sufficiently. In the well-characterized feeding neural circuit of , and appetitive OC increases neuronal excitability and electrical coupling among several neurons leading to an increase in expression of ingestive behavior. Here, we used the analog of OC to investigate whether OC reduces the excitability of a neuron, B4, whose inhibitory connections decrease expression of ingestive behavior. We found OC decreased the excitability of B4. This change appeared intrinsic to B4 because it could be replicated with an analog of OC in isolated cultures of B4 neurons. In addition to changes in B4 excitability, OC decreased the strength of B4's inhibitory connection to a key decision-making neuron, B51. The OC-induced changes were specific without affecting the excitability of another neuron critical for feeding behavior, B8, or the B4-to-B8 inhibitory connection. A conductance-based circuit model indicated that reducing the B4-to-B51 synapse, or increasing B51 excitability, mediated the OC phenotype more effectively than did decreasing B4 excitability. We combined these modifications to examine whether they could act synergistically. Combinations including B51 synergistically enhanced feeding. Taken together, these results suggest modifications of diverse loci work synergistically to mediate OC and that some neurons are well suited to work synergistically with plasticity in other loci. The ways in which synergism of diverse plasticity loci mediate the change in motor patterns in operant conditioning (OC) are poorly understood. Here, we found that OC was in part mediated by decreasing the intrinsic excitability of a critical neuron of feeding behavior, and specifically reducing the strength of one of its inhibitory connections that targets 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 is mediated by dopamine (DA), the present study provides insights into specific and synergistic mechanisms of DA-mediated reinforcement of behaviors.
尽管有许多研究探讨了操作性条件作用（OC）的机制，但 OC 可塑性基因座的多样性及其协同作用尚未得到充分研究。在 的典型摄食神经回路中， 和 奖赏性 OC 增加了神经元的兴奋性和几个神经元之间的电耦合，从而导致摄食行为的表达增加。在这里，我们使用 OC 的类似物来研究 OC 是否会降低神经元 B4 的兴奋性，而 B4 的抑制性连接会降低摄食行为的表达。我们发现 OC 降低了 B4 的兴奋性。这种变化似乎是 B4 固有的，因为它可以在 B4 神经元的分离培养物中用 OC 的类似物复制。除了 B4 兴奋性的变化外，OC 还降低了 B4 对关键决策神经元 B51 的抑制性连接的强度。OC 诱导的变化是特异性的，不会影响另一个对摄食行为至关重要的神经元 B8 或 B4 到 B8 的抑制性连接。基于电导率的电路模型表明，减少 B4 到 B51 突触，或增加 B51 的兴奋性，比降低 B4 的兴奋性更有效地介导 OC 表型。我们将这些修改结合起来，以检查它们是否可以协同作用。包括 B51 的组合协同增强了摄食行为。总的来说，这些结果表明，不同基因座的修饰协同作用介导 OC，并且一些神经元非常适合与其他基因座的可塑性协同作用。协同作用不同可塑性基因座来调节操作性条件作用（OC）中运动模式变化的方式知之甚少。在这里，我们发现 OC 的部分原因是通过降低摄食行为关键神经元 B4 的内在兴奋性来介导的，特别是通过降低其靶向关键决策神经元的抑制性连接之一的强度来介导的。基于电导率的计算模型表明，已知的可塑性基因座在介导与 OC 相关的行为变化方面表现出惊人的协同作用水平。这些结果强调了理解编码记忆的不同类型可塑性的多样性、特异性和协同作用的重要性。此外，由于 在 中的 OC 是由多巴胺（DA）介导的，因此本研究为理解 DA 介导的行为强化的特异性和协同机制提供了线索。
