Memory impairment in early sensorimotor deprived rats is associated with suppressed hippocampal neurogenesis and altered CREB signaling

Sensorimotor function is important for cognitive development; however, little experimental evidence exists to support this assumption. In this study we tested the hypothesis that altered cAMP response element binding (CREB) protein induction and activity-regulated cytoskeletal-associated gene (Arc) expression may underlie the suppression of hippocampal neurogenesis and memory impairment associated with early sensorimotor deprivation. Associated memory was evaluated in sensorimotor deprived (T) and sham operated (C) rats using a contextual fear-conditioning task. Hippocampal dentate gyrus (DG) neurogenesis was assessed by Brdu and NeuN labeling. Hippocampal DG CREB signaling was examined by measuring protein and mRNA levels of CREB and activity-regulated cytoskeletal-associated gene (Arc). Contextual freezing responses in the 1-day recall test were significantly lower in 25- and 35-day-old group T compared to C rats (P < 0.01), indicating that hippocampal-dependent memory impairment was caused by early sensorimotor deprivation. Furthermore, group T rats exhibited significantly decreased CREB and Arc activation in the hippocampal DG at 25 and 35 days compared to in group C rats (P < 0.01 for both). These changes may underlie decreased neurogenesis and impaired memory. No significant between groups differences were apparent in 45- and 60-day-old rats. These results suggest that early sensorimotor deprivation may alter CREB signaling, decrease Arc activation, suppress neurogenesis and ultimately impair memory.