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A molecular insight into the dissociable regulation of associative learning and motivation by the synaptic protein neuroligin-1.
BMC Biology ( IF 5.4 ) Pub Date : 2020-09-14 , DOI: 10.1186/s12915-020-00848-7
Jiaqi Luo 1 , Jessica M Tan 1 , Jess Nithianantharajah 1
Affiliation  

In a changing environment, a challenge for the brain is to flexibly guide adaptive behavior towards survival. Complex behavior and the underlying neural computations emerge from the structural components of the brain across many levels: circuits, cells, and ultimately the signaling complex of proteins at synapses. In line with this logic, dynamic modification of synaptic strength or synaptic plasticity is widely considered the cellular level implementation for adaptive behavior such as learning and memory. Predominantly expressed at excitatory synapses, the postsynaptic cell-adhesion molecule neuroligin-1 (Nlgn1) forms trans-synaptic complexes with presynaptic neurexins. Extensive evidence supports that Nlgn1 is essential for NMDA receptor transmission and long-term potentiation (LTP), both of which are putative synaptic mechanisms underlying learning and memory. Here, employing a comprehensive battery of touchscreen-based cognitive assays, we asked whether impaired NMDA receptor transmission and LTP in mice lacking Nlgn1 does in fact disrupt decision-making. To this end, we addressed two key decision problems: (i) the ability to learn and exploit the associative structure of the environment and (ii) balancing the trade-off between potential rewards and costs, or positive and negative utilities of available actions. We found that the capacity to acquire complex associative structures and adjust learned associations was intact. However, loss of Nlgn1 alters motivation leading to a reduced willingness to overcome effort cost for reward and an increased willingness to exert effort to escape an aversive situation. We suggest Nlgn1 may be important for balancing the weighting on positive and negative utilities in reward-cost trade-off. Our findings update canonical views of this key synaptic molecule in behavior and suggest Nlgn1 may be essential for regulating distinct cognitive processes underlying action selection. Our data demonstrate that learning and motivational computations can be dissociated within the same animal model, from a detailed behavioral dissection. Further, these results highlight the complexities in mapping synaptic mechanisms to their behavioral consequences, and the future challenge to elucidate how complex behavior emerges through different levels of neural hardware.

中文翻译:

通过突触蛋白neuroligin-1对关联学习和动机的可分离调节的分子洞察力。

在不断变化的环境中,大脑面临的挑战是灵活地引导适应性行为走向生存。复杂的行为和潜在的神经计算从大脑的多个层次的结构组件中出现:电路,细胞,最后是突触中蛋白质的信号复合物。根据这种逻辑,广泛认为突触强度或突触可塑性的动态改变是针对诸如学习和记忆之类的适应行为的细胞水平的实现。突触后细胞粘附分子neuroligin-1(Nlgn1)主要在兴奋性突触中表达,与突触前神经素形成反式突触复合物。大量证据表明Nlgn1对于NMDA受体的传递和长期增强(LTP)至关重要,两者都是潜在的学习和记忆的突触机制。在这里,我们使用了一系列基于触摸屏的认知分析方法,我们询问缺乏Nlgn1的小鼠中NMDA受体传递和LTP受损是否确实会干扰决策。为此,我们解决了两个关键的决策问题:(i)学习和利用环境的关联结构的能力;(ii)平衡潜在奖励和成本之间的权衡,或者对可用行动的正面和负面效用进行权衡。我们发现获得复杂的联想结构和调整学习的联想的能力是完整的。但是,Nlgn1的丧失会改变动机,从而导致降低克服奖励努力成本的意愿和增强为摆脱厌恶状况付出努力的意愿。我们建议Nlgn1对于在奖励成本权衡中平衡正面和负面效用的权重可能很重要。我们的发现更新了这一关键突触分子在行为中的规范观点,并暗示Nlgn1可能对于调节行动选择基础的不同认知过程至关重要。我们的数据表明,可以从详细的行为剖析中将学习和动机计算分解到同一动物模型中。此外,这些结果凸显了将突触机制映射到其行为后果的复杂性,以及未来的挑战,以阐明复杂行为如何通过不同级别的神经硬件出现。我们的发现更新了这一关键突触分子在行为中的规范观点,并暗示Nlgn1可能对于调节行动选择基础的不同认知过程至关重要。我们的数据表明,可以从详细的行为剖析中将学习和动机计算分解到同一动物模型中。此外,这些结果凸显了将突触机制映射到其行为后果的复杂性,以及未来的挑战,以阐明复杂行为如何通过不同级别的神经硬件出现。我们的发现更新了这一关键突触分子在行为中的规范观点,并暗示Nlgn1可能对于调节行动选择基础的不同认知过程至关重要。我们的数据表明,可以从详细的行为剖析中将学习和动机计算分解到同一动物模型中。此外,这些结果凸显了将突触机制映射到其行为后果的复杂性,以及未来的挑战,以阐明复杂行为如何通过不同级别的神经硬件出现。
更新日期:2020-09-14
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