POSTNATAL CRITICAL WINDOWS LINK SENSORY AFFERENT MATURATION TO TASK-SPECIFIC ADULT BEHAVIOURS

During early postnatal life, sensory experience sculpts spinal somatosensory circuits. Primary afferent classes refine their terminals on staggered timelines, suggesting critical windows during which dorsal horn networks may be sensitive to altered activity. We hypothesised that increasing sensory input during defined postnatal windows would produce distinct, long-lasting effects on adult sensory and motor function.
To selectively enhance sensory input in vivo, TRPV1-Cre mice received an intraplantar injection (P0) of a Cre-dependent AAV encoding the excitatory hM3Dq-DREADD (or control). The DREADD ligand CNO was administered daily (i.p.) at one of three critical developmental periods: P8-12, P13-17, P18-22. In adulthood, hindlimb reflexes were assessed with innocuous and noxious tests. Motor performance was quantified using CatWalk-XT and beam walking, with kinematics extracted using pose estimation (SLEAP). To investigate circuit-level correlates, we recorded lumbar dorsal horn extracellular activity using Neuropixels probes and performed immunohistochemistry.
Chemogenetic TRPV1⁺ activation during P8-12 increased adult sensitivity to innocuous brush, consistent with disruption during a stage when tactile reflexes are being refined. In contrast, P13-17 stimulation caused deficits in motor coordination, aligning with a stage when coordinated locomotion becomes a key behavioural demand. Finally, stimulation during P18-22 impaired skilled locomotion, suggesting a later phase important for the acquisition and consolidation of fine motor control. Neuropixels recordings and immunohistochemistry confirmed timepoint-specific changes in dorsal horn evoked activity and neuronal organisation.
Together, these findings support the existence of sequential postnatal windows in which excess sensory drive biases dorsal horn circuits development toward lasting changes in adult sensory processing and motor behaviour.