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:** 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:** 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:** Performance across training sessions

##### Variables

* The variables are the same as figure_1d.

#### Fi...,