ReviewTranssynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity
Introduction
Seasonal changes of the environment that are critical to survival and reproduction have a pronounced effect on birds and essentially all other animals. It is therefore not surprising that seasonal plasticity of the adult brain has been observed in every vertebrate taxon (Tramontin and Brenowitz, 2000). The avian song control system provides the best model for studying the mechanisms and functional significance of seasonal plasticity in brain and behavior, with changes that are the most pronounced yet observed in any vertebrate model. Song is a learned stereotyped behavior that can be quantitatively analyzed, it is regulated by well-identified neural circuits, and testosterone (T) and its androgenic and estrogenic metabolites exert a strong influence on the morphology and physiology of these neural circuits.
Sex steroids released by the gonads or synthesized in the brain can serve various functions in the adult nervous system: (1) they activate neurons in sexually dimorphic brain regions to produce sex-typical behaviors; (2) hormones provide a means of restricting neural activity to appropriate environmental and physiological conditions, as seen in hormone-regulated growth of the song control system in birds early in the breeding season; and (3) secretion of steroids by the gonads and transport to the brain can coordinate neural and behavioral activation with reproductive physiology. An example of this latter role is the vernal enhancement of song production by T in male birds to attract and stimulate mates at the time of year when the reproductive axis is optimized for breeding in both sexes (Ball et al., 2003). Steroids may act directly on neurons to have these effects. Neurons in limbic and other regions of the brain often have nuclear and/or membrane-bound receptors for different steroids. It has become clear recently that steroids may also have indirect actions on brain regions through transsynaptic mechanisms, even if neurons in the target regions lack steroid receptors. Transsynaptic trophic effects of steroids have been demonstrated most clearly in the context of seasonal plasticity of the adult avian song system, and that will be the focus of this review.
Section snippets
The avian song control system
Song is a learned behavior that is widely produced among the 4000 species of oscine songbirds and in many other avian taxa (Catchpole and Slater, 2008). Songs have well-defined acoustic structures that are characteristic of each species. In most species that breed in temperate and high latitude regions, song is produced largely or only by males. In many tropical species, however, females also sing and may join with males in producing complex vocal duets. There is extensive taxonomic diversity
Seasonality of breeding and song behavior in birds
Photoperiod is the primary environmental factor that influences activation of the avian reproductive system. In arctic, temperate, and subtropical birds, breeding is usually restricted to spring and early summer. Reproduction may also be seasonal in tropical species in which there are seasonal changes in environmental factors such as rainfall that influence breeding. Song behavior occurs most often or only in the breeding season in most species.
Seasonal plasticity in the brain
Seasonal changes in brain structure were first reported in the song system of domestic Canaries (Serinus canarius) by Nottebohm (1981). The song control system provides the most pronounced example of seasonal plasticity in an adult brain, and is the leading model for study of this process.
Seasonal changes in song behavior are accompanied by changes in the morphology of song nuclei in essentially every seasonally breeding songbird species that has been examined, including Rufous-collared
Seasonal changes in song behavior
Seasonal changes in various aspects of song behavior accompany plasticity of the song circuits. In some species of birds, such as the Spotted Towhee (Pipilo maculatus) and Sedge Warbler (Acrocephalus schoenobaenus), song is produced only during the breeding season and is absent at other times of year. Other species, such as Song Sparrows, White-crowned Sparrows, and Canaries, sing throughout most of the year. Even in these year-round singers, however, song is produced at much higher rates
Adaptive value of seasonal plasticity
What is the adaptive value of the extensive seasonal changes observed in the song circuits? Regrowing the song system each spring must impose an energetic cost. Is the cost of such yearly growth outweighed by some advantage that is gained? Other hormone sensitive regions of the avian brain, such as the hippocampus, do not undergo the seasonal regression and growth characteristic of the song system (Lee et al., 2001).
One hypothesis of the benefit of seasonal plasticity was presented by Nottebohm
Sex steroid influences on seasonal plasticity
T and its metabolites influence the development of song behavior and the song control circuits in juvenile birds (Arnold, 2002). These hormones also regulate seasonal plasticity of the song system. The secretion and metabolism of sex steroids vary with season; plasma T levels in male birds are high during breeding, and low after breeding. These seasonal changes in circulating hormone levels modulate song production (most birds sing frequently in the breeding season, and less or not at all
Seasonal growth and regression of the song control circuits occur rapidly and sequentially
Field studies of wild birds show that growth of the song system occurs rapidly once plasma T levels first start to rise as day length increases in late winter, and precedes full seasonal reproductive development. (Smith et al., 1997, Tramontin et al., 2001). In a laboratory study of captive White-crowned Sparrows implanted with a systemic T pellet and exposed to a long day photoperiod to mimic breeding conditions, HVC grew to its full breeding size and neuron number increased from 90,000 to
Site(s) of hormone action
We can ask which nuclei within the song circuits are directly targeted to initiate growth; steroid receptors or their mRNA are present in all of the major song nuclei (Fig. 1). Some insight is provided by the observation that HVC grows rapidly and its efferent targets RA and X change more slowly (Thompson et al., 2007, Tramontin et al., 2000). This sequential pattern of growth raised the hypothesis that T initially acts directly on HVC, which subsequently stimulates growth of RA and X
Interactions between steroid hormones and neurotrophins
Androgens and estrogens may have similar trophic effects on the developing and adult brain as do neurotrophins such as brain-derived neurotrophic factor (BDNF), and act by common cellular and molecular mechanisms (Scharfman and MacLusky, 2006, Scharfman and Maclusky, 2005, Pluchino et al., 2013). These commonalities suggest that steroids can play an important role in regulating the expression of the genes for BDNF and its cognate tropomyosin receptor kinase B (trkB), and/or that steroids and
Anterograde trophic effects
The “classical” model of neurotrophin action is for these proteins to be synthesized by peripheral targets, taken up by axon terminals, and retrogradely transported to the cell bodies where signaling cascades that support neuronal survival are activated (Zweifel et al., 2005). This is the mode of action by which nerve-growth factor (NGF), the first growth factor to be discovered, stimulates neurite outgrowth from cultured chick sensory ganglia (Levi-Montalcini, 1998). Recently, however, it has
Retrograde trophic effects
T and its metabolites also have retrograde trophic effects in the song control circuit. The addition of new RA-projecting neurons to HVC of adult White-crowned Sparrows is influenced by the electrical activity of target neurons in RA. The spontaneous activity of RA neurons is high in breeding sparrows and low in non-breeding birds (Meitzen et al., 2007a, Meitzen et al., 2007b, Meitzen et al., 2009). As discussed above, androgen action on RA neurons is permissive for them to increase their
Summary and conclusions
A summary of some of the interactions between photoperiod, hormones, neurotrophins, neural circuits, and song behavior that characterize seasonal plasticity of the song control system is presented in Fig. 5. As daylength increases beyond a threshold level in late winter, the hypothalamic–pituitary–gonadal axis is stimulated. The testes begin to recrudesce and secrete increased levels of testosterone into the blood. Testosterone is transported to the brain, where it acts on cells in HVC. Steroid
Acknowledgment
Supported by NIH MH53032 and NS075331.
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