Sex-specific, rapid neuroestrogen fluctuations and neurophysiological actions in the songbird auditory forebrain

Abstract

Recent evidence shows that brain-derived steroids such as estrogens ("neuroestrogens") are controlled in a manner very similar to traditional neurotransmitters. The advent of in vivo microdialysis for steroids in songbirds has provided new information about the spatial and temporal dynamics of neuroestrogen changes in a region of the auditory cortex, the caudomedial nidopallium (NCM). Here, experiments using in vivo microdialysis demonstrate that neuroestradiol (E(2)) fluctuations occur within the auditory NCM during presentation of naturalistic auditory and visual stimuli in males but only to the presentation of auditory stimuli in females. These changes are acute (within 30 min) and appear to be specific to the NCM, because similar treatments elicit no changes in E(2) in a nearby mesopallial region or in circulating plasma. Further experiments coupling in vivo steroid microdialysis with extracellular recordings in NCM show that neuroestrogens rapidly boost auditory responses to song stimuli in females, similar to recent observations in males. We also find that the rapid actions of estradiol on auditory responses are fully mimicked by the cell membrane-impermeable estrogen biotinylestradiol, consistent with acute estrogen actions at the neuronal membrane. Thus we conclude that local and acute E(2) flux is regulated by convergent multimodal sensory input, and that this regulation appears to be sex-specific. Second, rapid changes in local E(2) levels in NCM have consequences for the modulation of auditory processing in females and males. Finally, the rapid actions of neuroestrogens on NCM auditory processing appear to be mediated by a nonclassical, membrane-bound estrogen receptor.

Frank Beach Award Winner: Steroids as neuromodulators of brain circuits and behavior

“…Therefore, locally-produced steroids like estrogens can contribute to the acute modulation and functional output of neural circuits. In support of this perspective, estrogens can have acute, minute-by-minute effects on sensory processing by acting within discrete forebrain circuits (Kis et al, 2001; Remage-Healey et al, 2010; Remage-Healey et al, 2012; Tremere et al, 2009; Tremere and Pinaud, 2011). …”

Rapid effects of estrogens on behavior: Environmental modulation and molecular mechanisms

“…Local administration of estradiol to the NCM caused rapid increases in NCM firing rate, whereas local administration of an estrogen receptor antagonist suppressed NCM firing rates [80, 81], suggesting that local estradiol may nongenomically mediate auditory perception. In support of this hypothesis, retrodialysis of estradiol conjugated to E6biotin (which is membrane impermeable) to the NCM increased HVC activity for the bird's own song, but not for conspecific song or white noise [82, 83]. This indicates that estradiol is most likely acting via membrane-bound, as opposed to nuclear, ER receptors in the avian brain to affect song perception.…”

The neuroprotective actions of oestradiol and oestrogen receptors

“…In the brains of birds and mammals, aromatase is involved in the regulation of synaptogenesis and synaptic plasticity 151,152 , neurogenesis 153,154 , reproductive behaviour 155 , aggressive behaviour 155 , pain processing 156,157 , auditory processing 158 , social communication 158 , affect and cognition [159][160][161] .…”

“…The synaptic location of aromatase, together with the rapid regulation of its activity by neurotransmitters, suggests that brain-derived oestradiol acts as a rapid neuromodulator in synaptic circuits 155,163 . Indeed, rapid changes in brain aromatase activity are linked to swift changes in synaptic function, neuronal activity and behaviour 155,158 . Thus, local oestradiol synthesis in the brain, modulated by rapid changes in aromatase activity, seems to play an important part in the regulation of brain function and behaviour under physiological conditions.…”