Dynamic variation in forebrain estradiol levels during song learning

Abstract

Estrogens shape brain circuits during development, and the capacity to synthesize estrogens locally has consequences for both sexual differentiation and the acute modulation of circuits during early learning. A recently-optimized method to detect and quantify fluctuations in brain estrogens in vivo provides a direct means to explore how brain estrogen production contributes to both differentiation and neuromodulation during development. Here, we use this method to test the hypothesis that neuroestrogens are sexually-differentiated as well as dynamically responsive to song tutoring (via passive video/audio playback) during the period of song learning in juvenile zebra finches. Our results show that baseline neuroestradiol levels in the caudal forebrain do not differ between males and females during an early critical masculinization window. Instead, we observe a prominent difference between males and females in baseline neuroestradiol that emerges during the subadult stage as animals approach sexual maturity. Second, we observe that fluctuating neuroestradiol levels during periods of passive song tutoring exhibit a markedly different profile in juveniles as compared to adults. Specifically, neuroestrogens in the caudal forebrain are elevated following (rather than during) tutor song exposure in both juvenile males and females, suggesting an important role for the early consolidation of tutor song memories. These results further reveal a circadian influence on the fluctuations in local neuroestrogens during sensory/cognitive tasks. Taken together, these findings uncover several unexpected features of brain estrogen synthesis in juvenile animals that may have implications for secondary masculinization as well as the consolidation of recent sensory experiences.

The importance of neural aromatization in the acquisition, recall, and integration of song and spatial memories in passerines

“…cognitive function, a result in agreement with studies detailed above indicating contextdependent and behavioral selectivity of local E 2 synthesis(Remage-Healey et al, 2008Chao et al, 2014).Experiments regarding the role of local E 2 synthesis in the hippocampus of songbirds have added to the growing literature on the utility of avian models in the study of intricate cognitive processes(Salwiczek et al, 2010). While there is a body of data indicating that aromatization in the hippocampus affects synaptic physiology, the mechanisms leading to the "spatiotemporal fidelity" are less well understood but are under examination(Balthazart and Ball, 2011;Remage-Healey et al, 2011a;Saldanha et al, 2011;Saldanha et al, 2012;Schlinger et al, 2014)…”

“…Interestingly, around the same developmental time period, baseline neural E 2 levels in the caudal forebrain do not differ and increase in similar ways in response to passive song tutoring in juvenile males and females. However, differences do emerge as animals approach sexual maturity (Chao et al, 2014). These structural and functional sexual dimorphisms of the songbird NCM are providing insight into the mechanisms of local and acute E 2 production and signaling (recently reviewed in Krentzel and Remage-Healey, 2015).…”

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

“…Despite the indications that neuroestrogens can masculinize the zebra finch song circuit in vitro (Holloway & Clayton, 2001), our recent microdialysis studies in juvenile zebra finches reveal that E2 levels in the NCM are undifferentiated between males and females during the critical masculinization window (Chao et al , 2014). Specifically, while E2 levels were statistically indistinguishable between males and females during the early sensory (25-35 dph) and sensorimotor (35-60 dph) age ranges, Chao et al (2014) observed a significant elevated in baseline E2 levels within NCM during the late juvenile period, prior to sexual maturity (Fig.…”

“…Specifically, while E2 levels were statistically indistinguishable between males and females during the early sensory (25-35 dph) and sensorimotor (35-60 dph) age ranges, Chao et al (2014) observed a significant elevated in baseline E2 levels within NCM during the late juvenile period, prior to sexual maturity (Fig. 2).…”

“…2). Therefore, while NCM accounts for the predominant source of nearby estrogen synthesis to the song circuit for potential masculinization, the local levels of E2 within NCM during parts of the critical masculinization period are undifferentiated between males and females (Chao et al , 2014). It therefore remains to be determined whether local estrogen microenvironments within the song pre-motor circuitry (HVC-RA) are differentiated between males and females during the masculinization window.…”