Neurochemical organization and experience‐dependent activation of estrogen‐associated circuits in the songbird auditory forebrain

Abstract

The classic steroid hormone estradiol is rapidly produced by central auditory neurons in the songbird brain and instantaneously modulates auditory coding to enhance the neural and behavioral discrimination of acoustic signals. Although these recent advances highlight novel roles for estradiol in the regulation of central auditory processing, current knowledge on the functional and neurochemical organization of estrogen-associated circuits, as well as the impact of sensory experience in these auditory forebrain networks, remains very limited. Here we show that both estrogen-producing and -sensitive neurons are highly expressed in the caudomedial nidopallium (NCM), the zebra finch analog of the mammalian auditory association cortex, but not other auditory forebrain areas. We further demonstrate that auditory experience primarily engages estrogen-producing, and to a lesser extent, estrogen-responsive neurons in NCM, that these neuronal populations moderately overlap, and that acute episodes of sensory experience do not quantitatively affect these circuits. Finally, we show that whereas estrogen-producing cells are neurochemically heterogenous, estrogen-sensitive neurons are primarily glutamatergic. These findings reveal the neurochemical and functional organization of estrogen-associated circuits in the auditory forebrain, demonstrate their activation and stability in response to sensory experience in behaving animals, and highlight estrogenic circuits as fundamental components of central networks supporting sensory processing.

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

“…Similarly, the receptor mediated mechanism is unclear at present. Co-expression of estrogen receptors as well as aromatase in forebrain auditory perceptive regions are well conserved in vertebrates such as fish (Forlano et al , 2005) and birds (Metzdorf et al , 1999) Co-expression studies have shown that in NCM that ERβ is expressed in the same cells as aromatase (Jeong et al , 2011) where ERα has little to no co-expression with aromatase (Metzdorf et al , 1999, Saldanha & Coomaralingam, 2005). Sex differences have not been found for either receptor expression in NCM.…”

Frank Beach Award Winner: Steroids as neuromodulators of brain circuits and behavior

“…2). The NCM is enriched in expression of the estrogen-synthesis enzyme aromatase (Jeong et al, 2011; Saldanha et al, 2000), and it is considered analogous to mammalian secondary auditory cortex (e.g., Bolhuis and Gahr, 2006; Wang et al, 2010). NCM is key for song recognition and discrimination (Boumans et al, 2008; Gobes and Bolhuis, 2007; Sanford et al, 2010; Yoder et al, 2012) and NCM sends information into sensorimotor HVC indirectly via two distinct pathways (NIf and CLM; see Fig.…”

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

“…In a separate study, fadrozole into the NCM of the left but not right hemisphere disrupts normal preference for a bird's own song over conspecific song and decreases E 2 levels, while E 2 into the left increased the electrophysiological activity of neurons to the bird's own song and forward/reverse conspecific songs (RemageHealey et al, 2010). Finally, song exposure appears to recruit E 2 -producing neurons in NCM more so than those that are responsive to E 2 (Jeong et al, 2011). Collectively, these studies…”

“…Calcium-dependent mechanisms also increase the production and release of E 2 in cells of NCM (Remage-Healey et al, 2011b). Glutamate agonists increase and antagonists decrease aromatase activity and E 2 production in hypothalamus and auditory forebrain (Remage-Healey et al, 2008Jeong et al, 2011). In the zebra finch hippocampus, aromatase and N-methyl-D-aspartate receptors are co-expressed in hippocampal neurons, and these glutamate receptors are detected pre-and postsynaptically .…”