Fig. 7

Schematic representation of time-dependent hippocampal alterations observed in the VPA model. The temporal trajectory of in vivo hippocampal synaptic alterations is mimicked in vitro by neurons cultured in the absence of glia. Hippocampal alterations in VPA animals develop after the neonatal period in vivo whereas the aberrant synaptic pattern of hippocampal neurons from VPA animals occurs after active synaptogenesis in vitro. Initially, neurons from VPA animals show preserved dendritic tree and synapse number according with developmental stage, but as differentiation proceeds they exhibit a smaller dendritic arbor and fewer glutamatergic synapses. In fact, the latter depicts distinctive features: smaller vesicular pool, fewer NMDA clusters, increased NCAM and reduced PSA-NCAM, which could contribute to a higher resistance to structural synaptic remodeling. On the other hand, hippocampal microglia proved to be unaltered in neonatal and juvenile VPA animals or in culture, suggesting it may not be primarily affected in the VPA model