Synaptogenesis in adult-generated hippocampal granule cells is affected by behavioral experiences

Abstract

Adult-generated hippocampal immature neurons play a functional role after integration in functional circuits. Previously, we found that hippocampus-dependent learning in Morris water maze affects survival of immature neurons, even before they are synaptically contacted. Beside learning, this task heavily engages animals in physical activity in form of swimming; physical activity enhances hippocampal neurogenesis. In this article, the effects of training in Morris water maze apparatus on the synapse formation onto new neurons in hippocampus dentate gyrus and on neuronal maturation were investigated in adult rats. Newborn cells were identified using retroviral GFP-expressing virus infusion. In the first week after virus infusion, rats were trained in Morris water maze apparatus in three different conditions (spatial learning, cue test, and swimming). Properties of immature neurons and their synaptic response to perforant pathway stimulation were electrophysiologically investigated early during neuronal maturation. In controls, newborn cells showing GABAergic and glutamatergic responses were found for the first time at 8 and 10 days after mitosis, respectively; no cell with glutamatergic response only was found. Twelve days after virus infusion almost all GFP-positive cells showed both synaptic responses. The main result we found was the anticipated appearance of GABAergic synapses at 6 days in learner, cued and swimmer rats, supported also by immunohistochemical result. Swimmer rats showed the highest percentage of GFP-positive neurons with glutamatergic response at 10 and 12 days postmitosis. Moreover, primary dendrites were more numerous at 7 days in learner, cued and swimmer rats and swimmer rats showed the greatest dendritic tree complexity at 10 days. Finally, voltage-dependent Ca(2+) current was found in a larger number of newborn neurons at 7 days postinfusion in learner, cued and swimmer rats. In conclusion, experiences involving physical activity contextualized in an exploring behavior affect synaptogenesis in adult-generated cells and their early stages of maturation.