Songbirds are outstanding models in the study

Songbirds are outstanding models in the study of vocal communication (Maney and Pinaud, 2011). Following the pioneering studies of William H. Thorpe and Peter Marler on the development of song in chaffinches (Fringilla coelebs) and white-crowned sparrows (Zonotrichia leucophrys) (Marler, 2004; Thorpe, 1954), Nottebohm and colleagues identified the neural network mediating song production in oscines (Nottebohm, 1980; Nottebohm et al., 1976). The auditory inputs to this circuitry were later described (Mello et al., 2004; Theunissen et al., 2008) and formed the basis of the functional studies of estrogens on audition. As already mentioned, Naringin mg receptors alpha and aromatase are expressed in the zebra finch (Taeniopygia guttata) inner ear (Noirot et al., 2009). They are also expressed together with estrogen receptor beta at high densities in a major telencephalic second-order auditory area of songbirds, the caudomedial nidopallium, NCM (Jeong et al., 2011; Metzdorf et al., 1999; Peterson et al., 2005; Saldanha and Coomaralingam, 2005; Saldanha et al., 2000). Additionally, the membrane G protein-coupled estrogen receptor GPER1, also known as GPR30, is expressed in broad areas of the zebra finch telencephalon (Acharya and Veney, 2012; Krentzel et al., 2018). Three types of evidence indicate that systemic estradiol presumably acting through these estrogen receptors regulate auditory sensitivity and selectivity. First, the auditory brainstem response (ABR) recorded immediately after the onset of auditory stimuli have an increased amplitude during the spring when circulating estradiol concentrations are high in a number of songbird species (Henry and Lucas, 2009; Lucas et al., 2007). Opposite effects have however been observed in white-breasted nuthatches (Sitta carolinensis) and downy woodpeckers (Picoides pubescens) (Lucas et al., 2002; Lucas et al., 2007). Seasonal plasticity thus seems to affect the peripheral auditory processing, possibly with estrogenic mediation of inner ear function (Caras, 2013). Accordingly, in another seasonal songbird, the Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii), in females in breeding condition (i.e. maintained under long day length and implanted with a subcutaneous estradiol pellet), the ABRs displayed elevated threshold and longer peak latencies compared to ABRs from females in non-breeding condition (short day length and no estradiol implant) (Caras et al., 2010). Secondly, this role of estrogens is confirmed by electrophysiological recording of neurons in telencephalic auditory areas. The comparison of extracellular single unit responses to pure tones or to conspecific songs in white-crowned sparrows (Zonotrichia leucophrys) brought into breeding or non-breeding condition as described above identified highly specific effects of estradiol (Caras et al., 2012). Estradiol increased the spontaneous firing rates, the maximally evoked firing rates and the auditory response strength across a wide range of stimuli specifically in one class of cells showing a monotonic response to stimuli. The response properties of these cells were additionally correlated with circulating estradiol concentrations. These effects were not present in the non-monotonic cells that display suppressed firing rates at higher sound intensities. Other studies based on single- and multi-units recordings in canaries (Serinus canaria) have additionally reported enhanced spontaneous activity and neural selectivity for the bird own song (BOS) as a function of season in the song control nucleus HVC (used as a proper name) that receives indirect auditory inputs from the telencephalic auditory areas (Del Negro and Edeline, 2002; Del Negro et al., 2000; Del Negro et al., 2005). Similarly in zebra finches, increases in neuroestrogens in the auditory area NCM enhance song selectivity in HVC whereas opposite effects are observed following inhibition of neuroestrogens production in NCM (Remage-Healey and Joshi, 2012).