Functional maturation of thalamic reticular nucleus during early postnatal development

The thalamic reticular nucleus (TRN) is the principal inhibitory source of thalamus, it consists of GABAergic neurons that receive collateral projections from the thalamus and cortex but send their inhibition only to the thalamus, playing a key role in thalamocortical (TC) network modulation. TRN participates in generating thalamocortical slow waves and sleep spindles, as well as in attention, memory and sensory filtering, through different firing patterns. Maturation of the TRN-thalamus complex during early postnatal development is critical for the emergence of TC function. Although functional development of the TRN has been explored, an extensive characterization of firing patterns maturation across the first postnatal weeks was still lacking, as well as an integral analysis of developmental trajectories. Using whole-cell patch-clamp recordings in mice across five developmental stages, we provide a systematic electrophysiological profile of TRN maturation during the first three postnatal weeks. Our data show a protracted developmental trajectory of TRN, encompassing passive membrane and action potential properties, as well as tonic and burst firing patterns, the latter essential for sleep wave generation in the mature thalamocortical network. Passive membrane properties stabilize by P10, action potentials reach adult-like characteristics at P14, and tonic and burst firing patterns continue to mature until P21. Spontaneous excitatory postsynaptic currents evolve in parallel and largely stabilize at P14. Together, these findings identify critical periods in the development of thalamic inhibitory pathways and provide a framework for understanding how altered maturation trajectories may contribute to neurodevelopmental disorders.