Abstract
Early life stress (ELS) and adversity influences neurodevelopmental trajectories and affects maturation of brain circuits, network connectivity and epigenetic regulation, leading to increased vulnerability to adult psychopathology. ELS timing targets sensitive periods for neural plasticity, which are identified by the ability to reach physical and sensorimotor developmental milestones. In particular, motor development, being highly dependent on coordinated activity across several brain regions, is especially susceptible to environmental challenges, although detailed modifications are unclear. Here we used the limited bedding (LB) paradigm in rats to examine the effects of ELS longitudinally on physical and sensorimotor milestones as well as morphological changes in the motor cortex (M1) and motor behavior in male and female juveniles. Neonates from the LB litters displayed delayed eye opening and reduced weight gain compared to NB pups. Reaching sensory milestones such as cliff avoidance, ear twitch and auditory startle responses was delayed by LB exposure, similarly to surface righting reflex, grasping reflex and orienting behavior that were significantly impaired in both male and female LB pups. In juvenile LB rats, locomotion in the openfield was reduced and hind limb gait was impaired. There were no bedding or sex effects on skilled walking. Morphological analysis of Layer V motor cortex neurons (M1) in juveniles revealed that LB reduced dendritic length and increased spine density, but in females only. These data show that LB exposure during the neonatal period delays the reaching of multiple developmental milestones in several domains associated with the maturation of motor function and coordination.