Stress is considered a potent environmental risk factor for many behavioral abnormalities, including anxiety and mood disorders 1,2 . Animal models can exhibit limited but quantifiable behavioral impairments resulting from chronic stress, including deficits in motivation, abnormal responses to behavioral challenges, and anhedonia 3-5 . The hippocampus is thought to negatively regulate the stress response and to mediate various cognitive and mnemonic aspects of stressinduced impairments 2,3,5 , though the neuronal underpinnings sufficient to support behavioral improvements are largely unknown. Here, we acutely rescue stress-induced, depression-related behaviors by optogenetically reactivating DG cells that were previously active during a positive experience. A brain-wide histological investigation, coupled with pharmacological and projectionspecific optogenetic blockade experiments, identified glutamatergic activity in the hippocampusamygdala-nucleus accumbens pathway as a candidate circuit supporting the acute rescue. Finally, chronically reactivating hippocampal cells associated with a positive memory resulted in a rescue of stress-induced behavioral impairments and neurogenesis at time points beyond the light stimulation. Together, our data suggest that activating positive memories artificially is sufficient to suppress depression-like behaviors and point to DG engram cells as potential therapeutic nodes for intervening with maladaptive behavioral states.Our recent studies have demonstrated that DG cells that express c-Fos during fear or reward conditioning define an active neural population that is sufficient to elicit both aversive and Reprints and permissions information is available at www.nature.com/reprints.

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP.

Purpose Spastic cerebral palsy (CP) is characterized by four neuromuscular deficits: weakness, short muscle-tendon unit, muscle spasticity and impaired selective motor control (SMC). We examined the influence of impaired SMC on gait in children with bilateral spastic CP. Delineating the influence of neuromuscular deficits on gait abnormalities can guide surgical and therapeutic interventions to reduce long-term debilitating effects of CP. Methods The relationship between impaired SMC and gait was assessed using multivariate linear regression analysis of Selective Control Assessment of the Lower Extremity (SCALE) in relation to stance phase knee flexion and temporal-spatial gait parameters calculated using 3D kinematics for 57 children with bilateral spastic CP, ages seven to 11 years. Results Mean SCALE values were 5.8 (0 to 10, sd 3.0) and 5.7 (0 to 10, sd 2.9) for right and left legs, respectively. Multivariate linear regression models, including right and left SCALE and height, significantly predicted right and left knee flexion at initial contact (R = 0.479, p = 0.003; R = 0.452, p = 0.007, respectively) and right and left knee flexion in midstance (R = 0.428, p = 0.013; R = 0.407, p = 0.022, respectively). The model significantly predicted right and left step length (R = 0.645, p = 0.000; R = 0.523, p = 0.001, respectively) and predicted gait velocity (R = 0.444, p = 0.008). The model including SCALE did not predict step width. Conclusion Results indicate impaired SMC predicts increased knee flexion at initial contact, and reduces step length and velocity. Understanding the influence of impaired SMC on gait can inform decisions regarding therapy and surgery, such as hamstring lengthening. Level of evidence Level II Retrospective Study