The estrogen (E) synthetic enzyme aromatase is localized in presynaptic boutons of many vertebrates including humans. In songbirds and rodents, E-receptors at postsynaptic loci support the idea that synaptocrine hormone provision is a bona fide method of steroid delivery. Thus, with prior support we have established the incidence, prevalence, and potential mechanism of action of synaptically produced E. The songbird affords unparalleled advantages towards the further understanding of synaptocrinology. In the zebra finch, synaptic aromatase comprises about half of all aromatase activity in the brain. In contrast to all other species studied, synaptic aromatase is abundant in areas with no somal aromatase. Thus, the specific contribution of synaptic E to local steroid levels in the brain can be easily studied. Presynaptic aromatase is higher in males relative to females, suggesting a sex- associated, behavioral role for synaptic hormone provision. However, we know very little about the how synaptic E contributes to local E levels, how synaptic E may be regulated, and what role synaptic E plays in brain physiology. Using recently developed sensitive measurements of steroid levels, I will specifically test how local brain levels of E are affected by synaptic aromatization. Then, using electron-microscopy, I will test which parts of the brain contribute to local E levels by identifying the projection neurons that contain synaptic aromatase. Lastly, with established behavioral paradigms, I will test the role of synaptic aromatization on the mechanisms of learning and memory. These studies will greatly increase our understanding of how synaptocrine E contributes to the hormonal, electrical, and behavioral functioning of the vertebrate brain. This work, supported by NS 047267, suggests a coupling of chemical and electrical signaling. The abundance and exclusivity of synaptic aromatase in brain areas known to modulate behavior, make the songbird an excellent model to understand this novel mechanism in neuroendocrinology.

Public Health Relevance

In humans and other animals, estrogen affects many structural and functional endpoints by its action on the nervous system. These endpoints include aggression, mood, balance, neuroprotection, and learning. How estrogens are provided to discrete brain areas is a field of intense investigation. Estrogen is synthesized in presynaptic boutons of humans, rodents, and songbirds. In previously supported work we have learned that synaptic estrogen synthesis is abundant and localized within brain areas important for learning and plasticity in the songbird brain. The proposed experiments seek to understand the contribution of synaptically produced estrogen to local brain areas, their source, and their physiological function. These studies are critical in order to evaluate the role of synaptic estrogen in learning, memory, and neuroprotection. This will greatly inform therapeutic advances in the treatment of diseases that involve the loss of memory and brain degeneration such as Alzheimer's, Parkinson's, and stroke.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Gnadt, James W
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American University
Schools of Arts and Sciences
United States
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Mehos, C J; Nelson, L H; Saldanha, C J (2016) A Quantification of the Injury-Induced Changes in Central Aromatase, Oestrogenic Milieu and Steroid Receptor Expression in the Zebra Finch. J Neuroendocrinol 28:12348
Bailey, David J; Saldanha, Colin J (2015) The importance of neural aromatization in the acquisition, recall, and integration of song and spatial memories in passerines. Horm Behav 74:116-24
Duncan, Kelli A; Walters, Bradley J; Saldanha, Colin J (2013) Traumatized and inflamed--but resilient: glial aromatization and the avian brain. Horm Behav 63:208-15
Cornil, Charlotte A; Leung, Cary H; Pletcher, Eric R et al. (2012) Acute and specific modulation of presynaptic aromatization in the vertebrate brain. Endocrinology 153:2562-7
Ash, Ashley L; Saldanha, Colin J; Bailey, David J (2012) Calbindin-D28K expression increases in the dorsolateral hippocampus following corticosterone treatment in female zebra finches (Taeniopygia guttata). Hippocampus 22:510-5
Duncan, Kelli A; Saldanha, Colin J (2011) Neuroinflammation induces glial aromatase expression in the uninjured songbird brain. J Neuroinflammation 8:81
Remage-Healey, Luke; Saldanha, Colin J; Schlinger, Barney A (2011) Estradiol synthesis and action at the synapse: evidence for ""synaptocrine"" signaling. Front Endocrinol (Lausanne) 2:28
Saldanha, Colin J; Remage-Healey, Luke; Schlinger, Barney A (2011) Synaptocrine signaling: steroid synthesis and action at the synapse. Endocr Rev 32:532-49
Walters, Bradley J; Alexiades, Nikita G; Saldanha, Colin J (2011) Intracerebral estrogen provision increases cytogenesis and neurogenesis in the injured zebra finch brain. Dev Neurobiol 71:170-81
Charlier, T D; Newman, A E M; Heimovics, S A et al. (2011) Rapid effects of aggressive interactions on aromatase activity and oestradiol in discrete brain regions of wild male white-crowned sparrows. J Neuroendocrinol 23:742-53

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