Administration of Anastrozole to Ovariectomized Rats Impairs Working Memoryin Association with Plastic Changes to Dendritic Spines on Prefrontal Third-layerPyramidal Neurons

Abstract

Gonadal estrogens influence several neurobiological events related to synaptic plasticity underlying cognitive behavior. Likewise, estradiol synthesized in neurons affects aspects of brain organization associated with cognition. Here, plastic changes to dendritic spines on third-layer pyramidal neurons from the prefrontal cortex of ovariectomized, anastrozole-treated female rats were studied. Anastrozole treatment dampened the efficiency of rats in resolving a spatial working memory test in the “Y” maze when compared with ovariectomized control and proestrus female rats. In addition, the administration of Anastrozole led to an increase in dendritic spines and filopodia on the pyramidal cells studied. The thin, mushroom, stubby and wide spines remained unchanged. Since filopodia are considered to be the precursors of novel spines, the increase in dendritic spines is consistent with the increase in filopodia. However, this was clearly insufficient to drive proper working memory performance, despite the apparent stability in the translation of synaptic information suggested by the similar spine types evident in the ovariectomized controls and the increases observed. These findings show that brain-derived estradiol is necessary for prefrontal activity to account for working memory performance. Further studies will be needed to elucidate the mechanisms underlying such spine enhancement in the absence of estradiol-mediated modulation of plasticity.