A study of juvenile-to-adult refinement of thalamic reticular circuits via LRRTM3 enables high-resolution sensory encoding. Dongsu Lee and Kyung Ah Han et al.

In the study, we identified LRRTM3, as an excitatory synapse-specific cell-adhesion molecules, that regulates the TRN circuit maturation. Using single-nucleus RNA sequencing, ex vivo and in vivo electrophysiology, immunohistochemistry, and behavioral assays with TRN-specific Lrrtm3 conditional knockout mice, we show that TRN-LRRTM3 modulates CT-TRN synaptic connectivity in a developmentally dynamic manner, maintains the excitation-inhibition (E/I) balance required for sensory processing, and thalamic sensory tuning for tactile discrimination. Also, we uncover a post-critical period refinement by distinct extracellular interactions of LRRTM3 across post-juvenile stages. Our findings redefine the TRN dynamically tuned circuit after the classical critical period. These results offer a framework for understanding how inhibitory circuit maturation may contribute to sensory processing after early development stage.
We performed single nucleus RNA-sequencing (snRNA-seq) to profile the thalamus of 6-and 15-weeks-old C57BL/6 mice. Single-nucleus transcriptomes of murine thalamic nuclei were generated using a fixative-exchange sequencing (FX-seq) workflow combined with sci-RNA-seq3 combinatorial barcoding. Thalamic tissues from 6- and 15-week-old C57BL/6 mice were perfusion-fixed, cryosectioned, crosslinked with a regioselective nucleobase crosslinker, enzymatically digested, and processed to isolate intact nuclei.