Neural aromatization accelerates the acquisition of spatial memory via an influence on the songbird hippocampus Joseph G. Oberlander, a Barney A. Schlinger, b,c Nicola S. Clayton, d and Colin J. Saldanha a, * a Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, USA b Physiological Science, BRI, UCLA, Los Angeles, CA 90095, USA c Laboratory of Neuroendocrinology, BRI, UCLA, Los Angeles, CA 90095, USA d Experimental Psychology, University of Cambridge, Cambridge, UK Received 7 July 2003; revised 12 December 2003; accepted 16 December 2003 Abstract Circulating estrogens affect the neural circuits that underlie learning and memory in several vertebrates via an influence on the hippocampus. In the songbird hippocampus local estrogen synthesis due to the abundant expression of aromatase may modulate hippocampal function including spatial memory performance. Here, we examined the effect of estradiol, testosterone, and dihydrotestosterone on the structure and function of the songbird hippocampus. Adult male zebra finches were castrated, implanted with one of these steroids or a blank implant, and trained on a spatial memory task. The rate of acquisition and overall performance on this task was recorded by direct observation. The size and density of cells in the hippocampus and its volume were measured. Estradiol-treated birds learned the task more rapidly than any other group. Although testosterone- and blank-implanted birds did learn the task, we found no evidence of learning in dihydrotestosterone-implanted subjects. Cells in the rostral hippocampus were larger in estradiol- and testosterone-treated birds relative to other groups. A corresponding decrease in the density of cells was apparent in estradiol-implanted subjects relative to all other groups. These data suggest that estradiol may accelerate the acquisition of a spatial memory task and increase the size of neurons in the rostral hippocampus. Since testosterone-mediated changes in acquisition and cell size were similar to those of estradiol, but not dihydrotestosterone, we conclude that neural aromatization of testosterone to estrogen is responsible for effects on the structure and function of the songbird hippocampus. D 2004 Elsevier Inc. All rights reserved. Keywords: Estrogen; Testosterone; Aromatase; Zebra finch; Dihydrotestosterone; Synapse Introduction Estrogenic enhancement of memory performance has been reported in several vertebrates including humans (Sherwin, 1996), non-human primates (Bellino and Wise, 2003), and murine rodents (Gibbs, 1998; McEwen, 1994; Woolley et al., 1997). Enhancement of memory perfor- mance seems to occur via the potent activational effects of estradiol (E 2 ) on the hippocampus (HP). More specifically, in rodents, exogenous E 2 increases the number of dendritic spines on HP neurons and the number of synapses onto these dendritic spines (Murphy and Segal, 1996; Woolley and McEwen, 1994; Yankova et al., 2001). Corresponding changes in HP neuronal function have also been observed including enhancements in synaptic transmission and spatial memory performance (Gibbs, 1998; Woolley et al., 1997). Thus, HP structure and function are sensitive to estrogens in several vertebrates. In songbirds (order Passeriformes), in addition to periph- eral sources, the brain itself synthesizes E 2 due to the abundant expression of aromatase ( estrogen-synthase) (Schlinger and Arnold, 1991, 1992). Aromatase is especially enriched in the HP, a characteristic well conserved across every songbird species investigated (Fusani et al., 2000, 2001a,b; Metzdorf et al., 1999; Saldanha and Schlinger, 1997; Saldanha et al., 1998, 1999, 2000; Shen et al., 1994, 1995). Notably, HP aromatase is extremely low or undetect- able in adult non-songbirds and adult mammals (Roselli and Resko, 1997; Saldanha et al., 1998). Presumably, HP aroma- tization of testosterone provides high levels of local E 2 available to maintain the integrity and function of HP circuits. 0018-506X/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yhbeh.2003.12.003 * Corresponding author. Department of Biological Sciences, Lehigh University, 111 Research Drive, Bethlehem, PA 18015. Fax: +1-610- 758-4004. E-mail address: colin@lehigh.edu (C.J. Saldanha). www.elsevier.com/locate/yhbeh Hormones and Behavior 45 (2004) 250 – 258