Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an ‘interface’ nucleus

Abstract

Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher-order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity.

Sex differences and rapid estrogen signaling: A look at songbird audition

“…Steroid hormones have been shown to be essential for development and masculinization of the song circuit (Holloway & Clayton, 2001) as well as playing an important neuromodulatory role in auditory perception and discrimination in adults (Maney & Pinaud, 2011, Pawlisch & Remage-Healey, 2015, Pinaud & Tremere, 2012). A unique advantage of the zebra finch model is that it provides a vocal learner that breeds well in lab settings and exhibits pronounced neuronal steroidgenesis, leading to the direct examination of the relationship between neuronal steroids and vocal learning (Mello, 2014).…”

A sensorimotor area in the songbird brain is required for production of vocalizations in the song learning period of development

“…It is well known that auditory evoked activity in HVC is mediated mostly by Nif (Janata and Margoliash, , Cardin et al, ; Bauer et al, ; Roy and Mooney, ). Selective auditory responses propagate from Nif to HVC: interference with neuroestrogens (through infusions of Fadrozole, an inhibitor of aromatase activity and local blocker of estradiol synthesis) in NCM affects selective responses in both of these nuclei (Pawlisch and Remage‐Healey, ). Interestingly, the single‐unit selectivity for the bird's own song that is characteristic of Nif and HVC neurons is reduced after Fadrozole administration into NCM (Pawlisch and Remage‐Healey, ).…”

“…Selective auditory responses propagate from Nif to HVC: interference with neuroestrogens (through infusions of Fadrozole, an inhibitor of aromatase activity and local blocker of estradiol synthesis) in NCM affects selective responses in both of these nuclei (Pawlisch and Remage‐Healey, ). Interestingly, the single‐unit selectivity for the bird's own song that is characteristic of Nif and HVC neurons is reduced after Fadrozole administration into NCM (Pawlisch and Remage‐Healey, ). The NCM has been implicated in memory for tutor song; therefore, interactions between NCM and HVC, mediated by CM and Nif, may be necessary for formation of a ‘song template’ when the bird is listening to the song it will eventually imitate (Gobes and Bolhuis, ; Bauer et al, ; London and Clayton, ; Gobes et al, ; Bolhuis et al, ; Roberts et al, ).…”

Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbirds

“…HVC: The sensorimotor nucleus HVC contains a population of tutor-song-selective cells (Volman, 1993;Prather et al, 2008;Vallentin et al, 2016;Moseley et al, 2017) and receives E2-sensitive, indirect projections from NCM in part via the nucleus interfacialis of the nidopallium (Nif; Remage-Healey and Joshi, 2012;Pawlisch and Remage-Healey, 2015). To determine whether suppressing E2 synthesis in development affected downstream representations of either BOS or tutor song, we also recorded from HVC.…”