Medial septum-dependent encoding of contextual inputs by hippocampal splitter cells

The brain's ability to adapt to changing environments relies on encoding associations between stimuli and response strategies. Hippocampal splitter cells, which exhibit context-dependent firing patterns, are thought to contribute to this process, but whether they encode non-spatial contextual information and the neural circuits supporting such representations remain unclear. Using in vivo calcium imaging, we record dorsal hippocampal activity in mice performing a conditional discrimination task. Splitter cells encode both contextual input and response information in a dissociable manner, with their numbers and task-specific representations increasing during learning. Selective inhibition of the medial septum (MS) pathway or parvalbumin-expressing neurons in the MS reduces behavioral accuracy and decreases splitter cell numbers. MS inactivation specifically disrupts contextual representation without affecting response-related encoding. These findings demonstrate that splitter cells rely on distinct circuits to encode different components of the associative structure, with the MS critically supporting contextual inputs required for flexible behavior.大脑适应多变环境的能力，依赖于对刺激与反应策略之间关联的编码。海马分流细胞（splitter cells）是一类具有情境依赖性放电模式的细胞，被认为参与这一过程，但它们是否编码非空间情境信息，以及支撑这类表征的神经环路仍不明确。本研究采用在体钙成像（in vivo calcium imaging）技术，对执行条件性辨别任务（conditional discrimination task）的小鼠的背侧海马活动进行记录。结果显示，海马分流细胞以分离的方式编码情境输入与反应信息，其数量及任务特异性表征随学习进程不断增加。选择性抑制内侧隔核（medial septum, MS）通路或内侧隔核内的小白蛋白阳性神经元（parvalbumin-expressing neurons），会降低行为准确率并减少海马分流细胞的数量。内侧隔核失活会特异性破坏情境表征，但不影响与反应相关的编码过程。上述研究结果表明，海马分流细胞依赖不同的神经环路来编码关联结构的不同组分，而内侧隔核对支撑灵活行为所需的情境输入至关重要。