Regional vulnerability of the hippocampus to repeated motor activity deprivation

Spontaneous vertical and horizontal exploratory movements are integral components of rodent behavior. Little is known, however, about the structural and functional consequences of restricted spontaneous exploration. Here, we report two experiments to probe whether restriction in vertical activity (rearing) in rats could induce neuro-hormonal and behavioral disturbances. Rearing movements in rats were deprived for 3 h/day for 30 consecutive days by placing the animal into a circular tunnel task. Rats temporarily deprived of rearing behavior showed elevated plasma corticosterone levels but no detectable psychological distress and/or anxiety-related behavior within an elevated plus maze. However, rats emitted a greater number of 22-kHz ultrasonic vocalizations and spent significantly more time vocalizing than controls when deprived of their rearing behavior. Despite intact spatial performance within wet- and dry-land spatial tasks, rearing-deprived rats also exhibited a significant alteration in search strategies within both spatial tasks along with reduced volume and neuron number in the hippocampal subregion CA2. These data suggest a new approach to test the importance of free exploratory behavior in endocrine and structural manifestations. The results support a central role of the CA2 in spontaneous exploratory behavior and vulnerability to psychological stress. © 2015 Elsevier B.V

Regional differences in BDNF expression and behavior as a function of sex and enrichment type: oxytocin matters

The early environment is critical to brain development, but the relative contribution of physical versus social stimulation is unclear. Here, we investigated in male and female rats the response to early physical and social environmental enrichment in relation to oxytocin (OT) and brain-derived neurotrophic factor (BDNF) expression. The findings show that males and females respond differently to prolonged sensorimotor stimulation from postnatal days 21-110 in terms of functional, structural, and molecular changes in the hippocampus versus medial prefrontal cortex (mPFC). Physical enrichment promoted motor and cognitive functions and hippocampal BDNF mRNA and protein expression in both sexes. Combined physical and social enrichment, however, promoted functional and structural gain in females. These changes were accompanied by elevated plasma oxytocin (OT) levels and BDNF mRNA expression in the mPFC, while the hippocampus was not affected. Administration of an OT antagonist in females blocked the beneficial effects of enrichment and led to reduced cortical BDNF signaling. These findings suggest that an OT-based mechanism selectively stimulates a region-specific BDNF response which is dependent on the type of experience. © The Author(s) 2021