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Forebrain steroid levels fluctuate rapidly during social interactions

Abstract

Neurosteroids are powerful modulators of brain function and behavior, yet their dynamics in the brain have remained elusive. Using in vivo microdialysis in male zebra finches, we found that local estradiol levels increased rapidly in the forebrain during social interactions with females. Furthermore, when males were exposed to other males' songs, local estradiol levels also increased and testosterone levels dropped in a cortical/pallial auditory region that is analogous to mammalian auditory cortex. We also found that local estradiol and testosterone levels were differentially regulated in this same region by the conventional neurotransmitters glutamate and GABA, respectively. This study provides direct evidence that forebrain steroid levels are acutely and differentially regulated during social behavior in a region-specific manner and in a rapid time course similar to that of traditional neuromodulators.

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Figure 1: Validation of steroid microdialysis in zebra finches.
Figure 2: Expression of the immediate-early gene ZENK is upregulated in NCM during auditory stimulation, despite the presence of a microdialysis cannula and probe within NCM.
Figure 3: Estradiol injection causes a substantial and detectable increase in estradiol levels within NCM.
Figure 4: Fadrozole (100 μM, delivered via retrodialysis) significantly alters local steroid levels within NCM.
Figure 5: Local forebrain estradiol levels change rapidly within NCM during social interactions with females, while testosterone levels remain unchanged.
Figure 6: Local steroid levels within NCM change rapidly in response to acoustic playbacks.
Figure 7: Neurotransmitter activation causes acute changes in steroid levels within NCM.

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Acknowledgements

H. Lam provided technical support for microdialysis. M. Konishi provided the sound-attenuation chambers. I. Teramitsu and J. Goodson demonstrated surgical techniques. A. Briedbach, K. Faull and the staff of the University of California Los Angeles Pasarow GC/MS Core Facility (support from the National Science Foundation, CHE 0078299) provided technical support. N. Tillakaratne provided an ELISA plate reader. S. Cho assisted with tissue processing. C.I.M. Healey provided comments on the manuscript. This work was supported by the US National Institute of Neurological Disorders and Stroke (National Research Service Award F32NS058009-01) and the US National Institute of Mental Health (061994).

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L.R.-H. conducted the experiments and wrote the manuscript. N.T.M. provided methodological expertise and contributed to manuscript preparation. B.A.S. supervised the project and wrote the manuscript.

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Correspondence to Luke Remage-Healey.

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Remage-Healey, L., Maidment, N. & Schlinger, B. Forebrain steroid levels fluctuate rapidly during social interactions. Nat Neurosci 11, 1327–1334 (2008). https://doi.org/10.1038/nn.2200

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