The Journal of neuroscience : the official journal of the Society for Neuroscience

Changing neuroestrogens within the auditory forebrain rapidly transform stimulus selectivity in a downstream sensorimotor nucleus.

PMID 22699904


The activity of sensory circuits is shaped by neuromodulators, which can have downstream consequences for both sensorimotor integration and behavioral output. Recent evidence indicates that brain-derived estrogens ("neuroestrogens") can act as local circuit modulators in the songbird auditory forebrain. Specifically, neuroestrogens fluctuate in the auditory caudomedial nidopallium (NCM) during social interactions and in response to song stimuli. Within minutes of elevation, neuroestrogens also enhance auditory response properties of NCM neurons, and acute blockade of estrogen production in NCM disrupts behavioral song preferences. Here, we test the hypothesis that fluctuating neuroestrogens within NCM influence stimulus selectivity in a downstream sensorimotor nucleus (HVC, used as a proper name) that receives indirect auditory input from NCM. Dual extracellular recordings coupled with retrodialysis delivery show that song selectivity in HVC is rapidly enhanced by increasing neuroestrogens in NCM in adult males. Conversely, inhibiting neuroestrogen production in NCM causes a rapid decline in song selectivity in HVC, demonstrating the endogenous nature of this modulatory network. In contrast, HVC selectivity is unaffected by neuroestrogen delivery to either nearby caudomedial mesopallium or into HVC itself, indicating that neuroestrogen actions are restricted to NCM. In juvenile males, identical neuroestrogen treatment in NCM also does not alter HVC selectivity, consistent with a developmental maturation of the auditory network. Lastly, the rapid actions of estrogens leading to enhanced HVC selectivity appear to be mediated by membrane-bound receptors in NCM. These findings indicate that steroid-dependent modulation of sensory processing is not locally restricted and can be transmitted transynaptically to influence downstream sensorimotor and premotor targets.

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Fadrozole hydrochloride, ≥98% (HPLC)