DOI: 10.5061/dryad.44j0zpcth
title: Thalamocortical regulation of prefrontal stability enables abstract rule generalization

description: 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 specificity of thalamic regulation. These findings
 demonstrate that the MD stabilizes mPFC activity to enable the flexible
 transfer of abstract rules – a mechanism with broad implications for
 cognitive disorders and artificial intelligence.
description: # 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. #### File:
 figure_1g._sessions_to_criterion.xlsx **Description:** Number of training
 sessions required to reach criterion (75% correct) ##### Variables *
 column 1: the mice ID * column 2: session to criteria. * column 9: the
 mice ID * column 10: session to criteria. #### File: figure_3b.xlsx
 **Description:** Behavioral performance across the first three novel
 visual sessions ##### Variables * column 1: mice ID * column 2:
 performance with CNO * column 3: performance with saline #### File:
 figure_3d.xlsx **Description:** Behavioral performance across the first
 three novel visual sessions for photoinhibition of MD-to-mPFC terminals
 ##### Variables * column 1: mice ID * column 2: performance of mice with
 eNpHR * column 3: performance of mice with eYFP * column 5: performance of
 mice with eNpHR * column 6: performance of mice with eYFP * column 8:
 performance of mice with eNpHR * column 9: performance of mice with eYFP
 #### File: figure_3e.xlsx **Description:** Effects of MD-to-mPFC terminal
 inactivation during the sample ##### Variables * The variables are the
 same as figure_3d. #### File: figure_3f.xlsx **Description:** Effects of
 MD-to-mPFC terminal inactivation during the delay ##### Variables * The
 variables are the same as figure_3d. #### File: figure_3g.xlsx
 **Description:** Effects of MD-to-mPFC terminal inactivation during the
 choice ##### Variables * The variables are the same as figure_3d. ####
 File: figure_6a.xlsx **Description:** Percentage of correct trials in the
 novel visual task for mice with optogenetic activation of MD-to-mPFC
 projections, comparing light-OFF and light-ON conditions. ##### Variables
 * column 1: mice ID * column 2: performance with light off * column 3:
 performance with light on #### File: figure_6b.xlsx
 **Description:** Percentage of correct trials in the novel visual task for
 mice with optogenetic activation of mPFC, comparing light-OFF and light-ON
 conditions. ##### Variables * The variables are the same as figure_6a. ##
 Code/software Behavioral training, testing, and electrophysiological
 recording were controlled by custom MATLAB (MathWorks) software