BDNF-modulated plastic changes to dendritic spines in the hippocampus and prefrontal cortex underlie the NMDA-induced pre-convulsive stereotyped behavior in rats.

Systemic administration of NMDA induces stereotyped behavior followed frequently, but not always, by generalized epileptiform seizures. Increased NMDA activity provokes overstimulation of NMDA glutamate receptors in neurons with dendritic spines. Systemic administration of 100 mg/kg of NMDA i.p. induced stereotyped behavior in adult male rats 5-10 min post-injection. Then, the density and proportion of the various types of spines were counted in pyramidal neurons of the hippocampus and prefrontal cortex of two groups: NMDA-treated rats and a Saline control. Dendritic spine density increased in the experimental rats in both study regions, manifested in a higher proportion of stubby and wide (neckless) types. This type of spine showed a significant interaction between groups and brain structures. No changes were observed in the thin or mushroom spines. BDNF increased in the prefrontal cortex but remained unchanged in the hippocampus, suggesting that differential modulatory BDNF-mediated mechanisms are involved in synaptic plasticity in these two brain areas. The predominance of neckless (stubby, wide) spines suggests their involvement in synaptic overstimulation in both the hippocampus and prefrontal cortex. This possibility requires further research using diverse methodologies. This is the first study of the synaptic plasticity -mediated by dendritic spines- that underlie the pre-convulsive, stereotyped behavior in an experimental model based on epileptiform seizures.