Estradiol shapes auditory processing in the adult brain by regulating inhibitory transmission and plasticity-associated gene expression.
Estradiol impacts a wide variety of brain processes, including sex differentiation, mood, and learning. Here we show that estradiol regulates auditory processing of acoustic signals in the vertebrate brain, more specifically in the caudomedial nidopallium (NCM), the songbird analog of the mammalian auditory association cortex. Multielectrode recordings coupled with local pharmacological manipulations in awake animals reveal that both exogenous and locally generated estradiol increase auditory-evoked activity in NCM. This enhancement in neuronal responses is mediated by suppression of local inhibitory transmission. Surprisingly, we also found that estradiol is both necessary and sufficient for the induction of multiple mitogen-activated protein kinase (MAPK)-dependent genes thought to be required for synaptic plasticity and memorization of birdsong. Specifically, we show that local blockade of estrogen receptors or aromatase activity in awake birds decrease song-induced MAPK-dependent gene expression. Infusions of estradiol in acoustically isolated birds induce transcriptional activation of these genes to levels comparable with song-stimulated animals. Our results reveal acute and rapid nongenomic functions for estradiol in central auditory physiology and suggest that such roles may be ubiquitously expressed across sensory systems.
Department of Brain and Cognitive Sciences, University of Rochester, Rochester, New York 14627, USA.
Liisa A
LA
Tremere
Jin Kwon
JK
Jeong
Raphael
R
Pinaud
D000161:Acoustic Stimulation / Q000379:methods; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000733:Androstatrienes / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005260:Female; D046369:Finches; D005583:Fourier Analysis; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections / Q000379:methods; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011571:Psychoacoustics; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014851:Wakefulness
C115984:1,4,6-androstatrien-3,17-dione; D000733:Androstatrienes; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004967:Estrogens; D018756:GABA Antagonists; D017874:Immediate-Early Proteins; D013629:Tamoxifen; D004958:Estradiol; D020929:Mitogen-Activated Protein Kinase Kinases; D001640:Bicuculline