Medical Scientist Training Program, Emory University School of Medicine, Atlanta, GA, USA.
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
Nat Neurosci. 2022 Sep;25(9):1213-1224. doi: 10.1038/s41593-022-01148-9. Epub 2022 Aug 30.
Behavioral flexibility-that is, the ability to deviate from established behavioral sequences-is critical for navigating dynamic environments and requires the durable encoding and retrieval of new memories to guide future choice. The orbitofrontal cortex (OFC) supports outcome-guided behaviors. However, the coordinated neural circuitry and cellular mechanisms by which OFC connections sustain flexible learning and memory remain elusive. Here we demonstrate in mice that basolateral amygdala (BLA)→OFC projections bidirectionally control memory formation when familiar behaviors are unexpectedly not rewarded, whereas OFC→dorsomedial striatum (DMS) projections facilitate memory retrieval. OFC neuronal ensembles store a memory trace for newly learned information, which appears to be facilitated by circuit-specific dendritic spine plasticity and neurotrophin signaling within defined BLA-OFC-DMS connections and obstructed by cocaine. Thus, we describe the directional transmission of information within an integrated amygdalo-fronto-striatal circuit across time, whereby novel memories are encoded by BLA→OFC inputs, represented within OFC ensembles and retrieved via OFC→DMS outputs during future choice.
行为灵活性——即偏离既定行为序列的能力——对于在动态环境中导航至关重要，需要持久地编码和检索新记忆以指导未来的选择。眶额皮层（OFC）支持基于结果的行为。然而，协调的神经回路和细胞机制，通过这些机制，OFC 连接维持灵活的学习和记忆，仍然难以捉摸。在这里，我们在小鼠中证明，当熟悉的行为出乎意料地没有得到奖励时，基底外侧杏仁核（BLA）→OFC 投射双向控制记忆形成，而 OFC→背内侧纹状体（DMS）投射有助于记忆检索。OFC 神经元集合存储新学习信息的记忆痕迹，这似乎是由特定于回路的树突棘可塑性和神经生长因子信号转导在定义的 BLA-OFC-DMS 连接内促进的，而可卡因则阻碍了这一过程。因此，我们描述了在一个整合的杏仁核-额-纹状体回路中跨时间的信息的定向传递，在这个回路中，新的记忆通过 BLA→OFC 输入进行编码，在 OFC 集合中进行表示，并在未来的选择中通过 OFC→DMS 输出进行检索。
