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  • Another heroic set of studies

    2024-04-09

    Another heroic set of studies combining retrodialysis with electrophysiological recording at two distinct brain sites further indicated that the estradiol-induced increase in auditory-evoked firing in NCM also enhanced the selectivity of auditory-evoked responses in the downstream sensorimotor nucleus HVC (Remage-Healey and Joshi, 2012). Because NCM is not mono-synaptically connected to HVC, additional research was designed to investigate the pathway mediating this effect. This research demonstrated that the rapid effects of estrogens in NCM influence HVC via the nucleus interfacialis of the nidopallium (Nif) that has a direct input to HVC. Acute administration of estradiol to NCM increased the baseline firing rate and auditory-evoked firing rates in Nif while blockade of estradiol synthesis in NCM decreased selectivity of Nif and HVC neurons (Pawlisch and Remage-Healey, 2015). It was also shown that these changes in electrophysiological activity in NCM and HVC have functional consequences at the behavioral level. Retrodialysis of Fadrozole™ into the left NCM of awake male zebra finches caused within 30 min an acute suppression of their preference for their own song versus a conspecific song and after 30 min of wash-out the preference for the familiar versus unfamiliar song was restored. Surprisingly, no such effect was observed after retrodialysis of Fadrozole™ in the right NCM (Remage-Healey et al., 2010). A more recent study of this group revealed an age-dependent lateralisation of estradiol action on auditory processing in male zebra finches. More specifically, estradiol decreased auditory responsiveness in both hemispheres during the sensory phase of song learning, but estradiol increased auditory response in the right NCM and still decreased it in the left NCM during the sensorimotor phase (Vahaba et al., 2017). Given that previous studies in adult Ciprofibrate synthesis showed that inhibition of estrogens production in the left NCM suppresses burst firing of auditory neurons and interferes with proper song discrimination (Remage-Healey et al., 2010), it appears that there is an age-dependent shift in auditory processing and in its lateralized sensitivity to estrogens that would deserve further investigation. Taken together, all these data indicate that estrogens modulate auditory perception on songbirds by acting both at the level of the inner ear and in the telencephalic auditory area NCM.
    Functional magnetic resonance imaging for non-invasive studies of brain activity and its (hormonal) modulations To obtain a comprehensive understanding of the neuromodulatory impact of hormones, a careful selection of appropriate research strategies and techniques is crucial. As outlined above, most research on neuronal activity and its modulation by hormones in songbirds was so far performed using electrophysiology or immediate early gene techniques (ZENK, fos). These techniques are highly sensitive and specific, but they are invasive and/or constrained to a specific region of the brain. Therefore, they do not allow (1) to link changes in time of behavior with possible alterations in brain structure and function in the same bird and (2) to discern comprehensive neural network modulations over time within the same bird. In addition, it has been clearly demonstrated that any kind of brain injury induces expression of glial aromatase in both the songbird and mammalian brain (Garcia-Segura et al., 1999; Peterson et al., 2001; Saldanha et al., 2005). The simple fact of lowering an electrode or dialysis probe into the brain thus induces expression of the estrogen-synthesizing enzyme, which potentially confounds the results of studies analyzing actions of neuroestrogens. In contrast, in vivo imaging techniques and in particular fMRI is capable of overcoming these limitations and was proven appropriate and very promising for observing and further unraveling fast hormone actions in the brain. We will now briefly introduce the principles and the applicability of in vivo MRI as a novel tool that was first applied to the study of songbirds by our team in 1998 (Van der Linden et al., 1998). This has since then resulted in an extensive list of publications based on in vivo MRI studies of songbirds from our team often in collaboration with other songbird neuroscientists. These studies are dedicated to topics such as MRI atlases (De Groof et al., 2016; Gunturkun et al., 2013; Poirier et al., 2008; Vellema et al., 2011), or seasonal and hormone-driven neuroplasticity in canaries (Tindemans et al., 2003; Van der Linden et al., 2002) or starlings (De Groof et al., 2009; De Groof et al., 2008; Van der Linden et al., 2004; Van der Linden et al., 2002; Van Meir et al., 2004).