Environmental modulation of dendritic spine dynamics in mouse hippocampus

Ephrins and their tyrosine kinase receptors are involved in patterning of axonal connections during development in the nervous system of vertebrates [1]. They also play a role in neuronal plasticity in the adult brain, with particular reference to the hippocampus [2], in which they also modulate LTP induction [3]. We have raised C57/BL6 mice in an enriched environment, which increases adult hippocampal activity and alters hippocampal-dependent behaviors in rodents [4], to examine whether experience-dependent stimulation induces behavioral ameliorations, modifications in neuronal morphology and variations in the expression of ephrins, such as ephrin-B2 and eph-B2 receptor, in such structure. After an eight-week enrichment training, mice were challenged by the context-dependent fear conditioning test and Morris Water Maze, which are behavioral paradigms sensitive to hippocampal modifications [5], and by the cue-dependent fear conditioning test, which mainly relies on amygdala functions. Enriched mice (EM) performed better than non-enriched ones (CM) in the context-dependent fear conditioning and Morris Water Maze tests, but not in the cue-dependent fear conditioning test. After the enrichment period, dendritic arborization and spine density of Golgi-Cox stained CA1 hippocampal neurons were increased with respect to CM. After the fear conditioning testing however, spine density of EM hippocampal neurons decreased below the level of CM. Immunohistochemical analysis revealed a specific higher abundance of ephrin-B2 and eph-B2 receptor in the pyramidal layer of the CA1 area and in cortical layers, but not the amygdala, of EM. We suggest that: hippocampal neuron complexity is enhanced by enrichment along with spatial learning, but is rapidly decreased by an aversive experience; ephrin-B2 and eph-B2 receptor are involved in dendritic spine dinamycs during learning.