Gregory F. Ball

Revised Nomenclature for Avian Telencephalon and Some Related Brainstem Nuclei

The standard nomenclature that has been used for many telencephalic and related brainstem structures in birds is based on flawed assumptions of homology to mammals. In particular, the outdated terminology implies that most of the avian telencephalon is a hypertrophied basal ganglia, when it is now clear that most of the avian telencephalon is neurochemically, hodologically, and functionally comparable to the mammalian neocortex, claustrum, and pallial amygdala (all of which derive from the pallial sector of the developing telencephalon). Recognizing that this promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains, avian brain specialists began discussions to rectify this problem, culminating in the Avian Brain Nomenclature Forum held at Duke University in July 2002, which approved a new terminology for avian telencephalon and some allied brainstem cell groups. Details of this new terminology are presented here, as is a rationale for each name change and evidence for any homologies implied by the new names.

Photoperiodic Control of Seasonality in Birds

This review examines how birds use the annual cycle in photoperiod to ensure that seasonal events—breeding, molt, and song production—happen at the appropriate time of year. Differences in breeding strategies between birds and mammals reflect basic differences in biology. Avian breeding seasons tend to be of shorter duration and more asymmetric with respect to changes in photoperiod. Breeding seasons can occur at the same time each year (predictable) or at different times (opportunistic), depending on the food resource. In all cases, there is evidence for involvement of photoperiodic control, nonphotoperiodic control, and endogenous circannual rhythmicity. In predictable breeders (most nontropical species), photoperiod is the predominant proximate factor. Increasing photoperiods of spring stimulate secretion of gonadotropin-releasing hormone (GnRH) and consequent gonadal maturation. However, breeding ends before the return of short photoperiods. This is the consequence of a second effect of long photoperiods—the induction of photorefractoriness. This dual role of long photoperiods is required to impart the asymmetry in breeding seasons. Typically, gonadal regression through photorefractoriness is associated with a massive decrease in hypothalamic GnRH, essentially a reversal to a pre-pubertal condition. Although breeding seasons are primarily determined by photoperiodic control of GnRH neurons, prolactin may be important in determining the exact timing of gonadal regression. In tropical and opportunistic breeders, endogenous circannual rhythmicity may be more important. In such species, the reproductive system remains in a state of “readiness to breed” for a large part of the year, with nonphotic cues acting as proximate cues to time breeding. Circannual rhythmicity may result from a temporal sequence of different physiological states rather than a molecular or cellular mechanism as in circadian rhythmicity. Avian homologues of mammalian clock genes Per2, Per3, Clock, bmal1, and MOP4 have been cloned. At the molecular level, avian circadian clocks appear to function in a similar manner to those of mammals. Photoperiodic time measurement involves interaction between a circadian rhythm of photoinducibility and, unlike mammals, deep brain photoreceptors. The exact location of these remains unclear. Although the eyes and pineal generate a daily cycle in melatonin, this photoperiodic signal is not used to time seasonal breeding. Instead, photoperiodic responses appear to involve direct interaction between photoreceptors and GnRH neurons. Thyroid hormones are required in some way for this system to function. In addition to gonadal function, song production is also affected by photoperiod. Several of the nuclei involved in the song system show seasonal changes in volume, greater in spring than in the fall. The increase in volume is, in part, due to an increase in cell number as a result of neurogenesis. There is no seasonal change in the birth of neurons but rather in their survival. Testosterone and melatonin appear to work antagonistically in regulating volume.

Is brain estradiol a hormone or a neurotransmitter

Mounting evidence indicates that, besides their well-known hormonal mode of action at the genetic level, estrogens such as 17beta-estradiol also influence brain function by direct effects on neuronal membranes. Experimentally induced rapid changes in estradiol bioavailability in the brain have been shown to alter the expression of male sexual behavior significantly within minutes--probably too quickly to be accounted for by conventional genetic mechanisms. In parallel, recent studies indicate that aromatase, the enzyme that converts testosterone to estradiol in the brain, is expressed in presynaptic terminals and modulated within minutes by Ca(2+)-dependent phosphorylation. In this article, we develop the hypothesis that brain estrogens display many, if not all, functional characteristics of neuromodulators or even neurotransmitters.

Sex Differences in the Brain: The Not So Inconvenient Truth

### Introduction In 2001 the Institute of Medicine, a branch of the National Academy of Sciences in the U.S.A., concluded that many aspects of both normal and pathological brain functioning exhibit important yet poorly understood sex differences ([Wizemann and Pardu, 2001][1]). Ten years later, the

New Insights into the Regulation and Function of Brain Estrogen Synthase (Aromatase)

In the brain, conversion of androgens into estrogens by the enzyme aromatase (estrogen synthase) is a key mechanism by which testosterone regulates many physiological and behavioral processes, including the activation of male sexual behavior, brain sexual differentiation and negative feedback effects of steroid hormones on gonadotropin secretion. Studies on the distribution and regulation of brain aromatase have led to a new perspective on the control and function of this enzyme. A growing body of evidence indicates that the estrogen regulation of aromatase is, at least in part, trans-synaptic. Afferent catecholamine pathways appear to regulate aromatase activity in some brain areas and thereby provide a way for environmental cues to modulate this enzyme. The localization of aromatase in pre-synaptic boutons suggests possible roles for estrogens at the synapse.

Sexual differentiation of brain and behavior in birds

It is currently accepted that most sex differences in brain and behavior do not result from direct genomic actions, but develop following early exposure to a sexually differentiated endocrine milieu. In Japanese quail (Coturnix japonica), in contrast to rodents, the male reproductive phenotype appears to develop in the absence of endocrine influence, and estradiol secreted by the ovary of the female embryo is responsible for the physiologic demasculinization of females. In zebra finches (Taeniopygia guttata), estrogens administered early in life demasculinize copulatory behavior in males, but masculinize the vocal control regions in the brain and singing behavior of females. It is difficult to understand how these behaviors differentiate given that normal untreated males sing and copulate in a male-typical manner, whereas females never show these behaviors. All attempts to resolve this paradox with experiments based on the rodent model of sexual differentiation have been unsuccessful. We propose that copulatory behavior in zebra finches is differentiated in a manner similar to what has been described in quail, but that novel approaches need to be considered to understand the differentiation of the telencephalic song control system. In particular, the possible involvement of afferent input that may differentiate in a steroid-dependent or -independent manner should be thoroughly tested.

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

Changes in Plasma Levels of Luteinizing Hormone and Sex Steroid Hormones in Relation to Multiple-Broodedness and Nest-Site Density in Male Starlings

Changes in plasma levels of testosterone (T), progesterone (P), and luteinizing hormone (LH) were studied over the reproductive cycle in two double-brooded populations of European starlings (Sturnus vulgaris). In one population, nest sites (nest boxes) averaged 6 m apart (dense site), and in the other, nest boxes average 60 m apart (dispersed site). In both populations, plasma levels of T were high during the two egglaying stages when males were mate guarding and defending nest holes. A higher circulating level of T was observed during the first nesting attempt, when all pairs in possession of a box initiated clutches. Furthermore, plasma levels of T were higher in males nesting at the dense site compared with those in males at the dispersed site. Only about 30% of these pairs initiated second clutches after successfully rearing the first brood. Although plasma levels of T rose in males during the second clutch initiation, they were significantly lower than T levels measured during production of the first clutch. Circulating levels of LH became maximal during each egg-laying stage in a manner similar to those of T but did not vary as a function of nest-site density. Changes in circulating T were also examined in relation to a T-dependent secondary sexual characteristic, male bill color. We found that the seasonal change in bill color is sensitive to circulating levels of T only slightly above basal and much lower than those observed during times of male-male aggression. Circulating levels of P were constant from January to July, with no significant changes during the prebreeding and breeding periods. This is consistent with results of studies with captive males.

Neuroendocrinology of song behavior and avian brain plasticity: multiple sites of action of sex steroid hormones.

Seasonal changes in the brain of songbirds are one of the most dramatic examples of naturally occurring neuroplasticity that have been described in any vertebrate species. In males of temperate-zone songbird species, the volumes of several telencephalic nuclei that control song behavior are significantly larger in the spring than in the fall. These increases in volume are correlated with high rates of singing and high concentrations of testosterone in the plasma. Several song nuclei express either androgen receptors or estrogen receptors, therefore it is possible that testosterone acting via estrogenic or androgenic metabolites regulates song behavior by seasonally modulating the morphology of these song control nuclei. However, the causal links among these variables have not been established. Dissociations among high concentrations of testosterone, enlarged song nuclei, and high rates of singing behavior have been observed. Singing behavior itself can promote cellular changes associated with increases in the volume of the song control nuclei. Also, testosterone may stimulate song behavior by acting in brain regions outside of the song control system such as in the preoptic area or in catecholamine cell groups in the brainstem. Thus testosterone effects on neuroplasticity in the song system may be indirect in that behavioral activity stimulated by testosterone acting in sites that promote male sexual behavior could in turn promote morphological changes in the song system.

Androgen Receptor, Estrogen Receptor α, and Estrogen Receptorβ Show Distinct Patterns of Expression in Forebrain Song Control Nuclei of European Starlings1

In songbirds, singing behavior is controlled by a discrete network of interconnected brain nuclei known collectively as the song control system. Both the development of this system and the expression of singing behavior in adulthood are strongly influenced by sex steroid hormones. Although both androgenic and estrogenic steroids have effects, androgen receptors (AR) are more abundantly and widely expressed in song nuclei than are estrogen receptors (ERα). The recent cloning of a second form of the estrogen receptor in mammals, ERβ, raises the possibility that a second receptor subtype is present in songbirds and that estrogenic effects in the song system may be mediated via ERβ. We therefore cloned the ERβ complementary DNA (cDNA) from a European starling preoptic area-hypothalamic cDNA library and used in situ hybridization histochemistry to examine its expression in forebrain song nuclei, relative to the expression of AR and ERα messenger RNA (mRNA), in the adjacent brain sections. The starling ERβ cDNA...