Presynaptic N-methyl-D-aspartate receptor expression is increased by estrogen in an aromatase-rich area of the songbird hippocampus.

The vertebrate hippocampus (HP) is sensitive to estrogens, in part via effects on N-methyl-D-aspartate (NMDA)-type glutamate receptors (NR). Although the precise mechanism of this interaction is unclear, it constitutes a key interface in the plasticity of the adult vertebrate HP. The songbird HP expresses high levels of aromatase (estrogen synthase), suggesting that locally generated steroid may affect excitatory pathways. By using light, confocal, and electron microscopy with antibodies that specifically recognize aromatase and NR, we have 1) mapped their distribution in the zebra finch brain, 2) documented their coexpression in HP neurons, 3) studied the ultrastructure of NR-expressing cells in the HP, and 4) tested the influence of estrogen on the cellular and subcellular characteristics of NR-positive HP neurons. Aromatase and NR are coexpressed in HP neurons. NRs are detectable in presynaptic boutons of the songbird HP in addition to postsynaptic loci. Treatment with estrogen increased the somal size and innervation of NR-positive neurons and the frequency of presynaptic NR. Autoreception of excitatory neurotransmission via presynaptic NR may promote the strengthening of activity-dependent, excitatory synapses, thereby enhancing learning. NR-mediated autoreception may underlie estrogenic enhancement of HP structural and functional plasticity. Copyright 2004 Wiley-Liss, Inc.