McLachlan Caroline A, Lee David G, Kwon Osung, Delgado Kevin M, Manjrekar Nikita, Yao Zizhen, Zeng Hongkui, Tasic Bosiljka, Chen Jerry L
Department of Biology, Boston University, Boston, MA 02215, USA; Center for Neurophotonics, Boston University, Boston, MA 02215, USA.
Center for Neurophotonics, Boston University, Boston, MA 02215, USA; Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Cell Rep. 2025 Jan 28;44(1):115175. doi: 10.1016/j.celrep.2024.115175. Epub 2025 Jan 9.
Task learning involves learning associations between stimuli and outcomes and storing these relationships in memory. While this information can be reliably decoded from population activity, individual neurons encoding this representation can drift over time. The circuit or molecular mechanisms underlying this drift and its role in learning are unclear. We performed two-photon calcium imaging in the perirhinal cortex during task training. Using post hoc spatial transcriptomics, we measured immediate-early gene (IEG) expression and assigned monitored neurons to excitatory or inhibitory subtypes. We discovered an IEG-defined network spanning multiple subtypes that form stimulus-outcome associations. Targeted deletion of brain-derived neurotrophic factor in the perirhinal cortex disrupted IEG expression and impaired task learning. Representational drift slowed with prolonged training. Pre-existing representations were strengthened while stimulus-reward associations failed to form. Our findings reveal the cell types and molecules regulating long-term network stability that is permissive for task learning and memory allocation.
任务学习涉及学习刺激与结果之间的关联，并将这些关系存储在记忆中。虽然这些信息可以从群体活动中可靠地解码出来，但编码这种表征的单个神经元会随着时间的推移而发生漂移。这种漂移背后的神经回路或分子机制及其在学习中的作用尚不清楚。我们在任务训练期间对鼻周皮质进行了双光子钙成像。利用事后空间转录组学，我们测量了即刻早期基因（IEG）的表达，并将监测到的神经元分为兴奋性或抑制性亚型。我们发现了一个由IEG定义的网络，它跨越多个亚型，形成刺激-结果关联。在鼻周皮质中靶向缺失脑源性神经营养因子会破坏IEG表达并损害任务学习。随着训练时间的延长，表征漂移减缓。先前存在的表征得到加强，而刺激-奖励关联未能形成。我们的研究结果揭示了调节长期网络稳定性的细胞类型和分子，这种稳定性有利于任务学习和记忆分配。
