Thalamocortical regulation of prefrontal stability enables abstract rule generalization

The ability to generalize abstract rules to novel contexts is a hallmark of intelligent behavior, yet its neural mechanisms remain poorly understood. Here, we identify a thalamocortical circuit essential for abstract rule generalization in mice. Using a cross-modal delayed match-to-sample task, we find that mice generalize learned rules from auditory to visual domains, with the same medial prefrontal cortex (mPFC) neurons encode task rules across sensory modalities to enable generalization. Pathway-specific manipulations revealed that mediodorsal thalamus (MD) projections to the mPFC are causally required for generalization: optogenetic inhibition of MD-to-mPFC projections disrupts rule transfer by destabilizing mPFC representations, while enhancing this pathway improved performance. Strikingly, without MD input, mPFC recruits distinct neuronal populations for each task, abolishing cross-context stability. Conversely, direct mPFC excitation impairs generalization, highlighting the speci..., , # Thalamocortical regulation of prefrontal stability enables abstract rule generalization Dataset DOI: [10.5061/dryad.44j0zpcth](10.5061/dryad.44j0zpcth) ## Description of the data and file structure The behavioral, electrophysiological recording, and optogenetic manipulation data were collected. ### Files and variables #### File: figure_1d._auditory_DMS_DNMS_then_visual_DMS_DNMS.xlsx **Description:**Â Performance across training sessions ##### Variables * column 1: task name (DMS/DNMS: delayed match to sample/delayed nonmatch to sample) * column 2: training day * column 3-column 15: performance of mice 1-mice 13 #### File: figure_1e._visual_DMS_DNMS_then_auditory_DMS_DNMS.xlsx **Description:**Â Performance across training sessions ##### Variables * The variables are the same as figure_1d. #### File: figure_1f._auditory_go_nogo_then_visual_DMS_DNMS.xlsx **Description:**Â Performance across training sessions ##### Variables * The variables are the same as figure_1d. #### Fi...,将抽象规则泛化至全新情境的能力是智能行为的核心标志之一，但其神经机制至今仍未得到充分阐释。本研究首次鉴定出小鼠体内介导抽象规则泛化的关键丘脑皮层环路。 本研究采用跨模态延迟匹配样本任务（cross-modal delayed match-to-sample task），发现小鼠可将习得的规则从听觉领域泛化至视觉领域，且同一群内侧前额叶皮层（medial prefrontal cortex, mPFC）神经元能够跨感觉模态编码任务规则，从而支持规则泛化过程。 通路特异性操控实验表明，背内侧丘脑（mediodorsal thalamus, MD）向mPFC的投射是规则泛化的因果性必要条件：光遗传抑制MD至mPFC的投射会通过破坏mPFC神经表征的稳定性来阻断规则迁移，而增强该通路则可提升任务表现。值得注意的是，在缺乏MD输入的情况下，mPFC会为每一项任务招募不同的神经元群体，从而消除跨情境的表征稳定性。反之，直接激活mPFC会损害规则泛化能力，凸显了...（原文此处截断），# 丘脑皮层对前额叶稳定性的调控介导抽象规则泛化 数据集DOI：[10.5061/dryad.44j0zpcth](10.5061/dryad.44j0zpcth) ## 数据与文件结构说明 本研究收集了行为学、电生理记录以及光遗传操控相关实验数据。 ### 文件与变量说明 #### 文件：figure_1d._auditory_DMS_DNMS_then_visual_DMS_DNMS.xlsx **描述：** 各训练阶段的任务表现 ##### 变量说明 * 第1列：任务名称（DMS/DNMS：延迟匹配样本任务/延迟非匹配样本任务） * 第2列：训练天数 * 第3列至第15列：小鼠1至小鼠13的任务表现 #### 文件：figure_1e._visual_DMS_DNMS_then_auditory_DMS_DNMS.xlsx **描述：** 各训练阶段的任务表现 ##### 变量说明 * 变量设置与figure_1d文件完全一致 #### 文件：figure_1f._auditory_go_nogo_then_visual_DMS_DNMS.xlsx **描述：** 各训练阶段的任务表现 ##### 变量说明 * 变量设置与figure_1d文件完全一致 #### Fi...,