Submedius Thalamus Modulates Orbitofrontal Cortex Representations During Maternal Behavior in Mice

Abstract

The orbitofrontal cortex (OFC) is central to cognitive and social functions, yet its presynaptic partners remain incompletely defined. In female mice, the OFC modulates infant-directed maternal caregiving behaviors essential for offspring survival in an experience-dependent manner. Here, we identify the submedius thalamus (SMT) as a major presynaptic partner of the OFC. Trans-synaptic tracing revealed intensive inputs from both the SMT and mediodorsal thalamus (MD) to OFC layer 5 excitatory neurons. A mouse line Tnnt1-Cre enabled selective targeting of these higher-order thalamic nuclei. Axonal tracing demonstrated complementary projection patterns of SMT and MD across prefrontal regions. Microendoscopic Ca2+ imaging demonstrated pup retrieval encoding in SMT and MD, but only SMT exhibited learning-related plasticity, characterized by enhanced anticipatory responses as acquired maternal behaviors. Projection-specific chemogenetic silencing demonstrated that only SMT modulates OFC activity during pup retrieval. These findings demonstrate SMT as a previously uncharacterized thalamic hub shaping cortical representations of maternal behavior. HighlightsO_LIOFCRbp4 neurons receive strong inputs from higher-order thalamic nuclei (SMT, MD). C_LIO_LISMT and MD show complementary axonal projections across prefrontal cortical cortex. C_LIO_LISMT ensembles encode pup retrieval with experience-dependent plasticity. C_LIO_LISMT inputs selectively modulate pup retrieval representation in OFCRbp4 neurons. C_LI