Sonoko Ogawa

University of Tsukuba · School of Human Sciences

Oxytocin receptor (OXTR) modulates social behaviors in a species-specific manner. Remarkable inter- and intraspecies variation in brain OXTR distribution are associated with diversity in social behavior. To investigate potential genetic mechanisms underlying the phylogenetic plasticity in brain Oxtr expression and its consequences on social behavio...

Estrogen receptors (ERα and ERβ) are crucial for the regulation of socio-sexual behaviors and for the organization of sex-specific neural networks in the developing brain. However, how the distribution patterns of ERα and ERβ change throughout life is unclear. Using genetically modified ERβ-RFPtg mice, we investigated the distribution of ERα, ERβ,...

The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse (“social instigation”) resulting in heightened intermale aggression. Both chemogenetic and optogeneti...

Heightened aggressive behavior is considered as one of the central symptoms of many neuropsychiatric disorders including autism, schizophrenia, and dementia. The consequences of aggression pose a heavy burden on patients and their families and clinicians. Unfortunately, we have limited treatment options for aggression and lack mechanistic insight i...

Post-translational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, more than 150 human GPI anchored proteins have been discovered and about 30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian GPI. Phosphatidylinositol glycan biosy...

Post-translational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, more than 150 human GPI anchored proteins have been discovered and about 30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian GPI. Phosphatidylinositol glycan biosy...

Two types of nuclear estrogen receptors, ERα and ERβ, have been shown to be differentially involved in the regulation of various types of behaviors. Due to a lack of tools for identifying ERβ expression, detailed anatomical distribution and neurochemical characteristics of ERβ expressing cells and cellular co-expression with ERα remain unclear. We...

A clue to hippocampal function has been the discovery of place cells, leading to the ‘spatial map’ theory. Although the firing attributes of place cells are well documented, little is known about the organization of the spatial map. Unit recording studies, thus far, have reported a low coherence between neighboring cells and geometric space, leadin...

Estrogens receptors (ER) are involved in several sociosexual behaviors and fear responses. In particular, the ERα is important for sexual behaviors, whereas ERβ modulates anxiolytic responses. Using shRNA directed either against the ERα or the ERβ RNAs (or containing luciferase control) encoded within an adeno-associated viral vector, we silenced t...

The central part of the medial preoptic nucleus (MPNc) is associated with sexual arousal induction in male rats. However, it is largely unclear how males are sexually aroused and achieve their first copulation. We previously reported that more MPNc neurons activate during the first copulation than the second copulation. In this study, to explore th...

Acquisition of social dominance is important for social species including mice, for preferential access to foods and mates. Male mice establish social rank through agonistic behaviors, which are regulated by gonadal steroid hormone, testosterone, as its original form and aromatized form. It is well known that estrogen receptors (ERs), particularly...

It has long been known that the estrogen, 17β-estradiol (17β-E), plays a central role for female reproductive physiology and behavior. Numerous studies have established the neurochemical and molecular basis of estrogenic induction of female sexual behavior, i.e., lordosis, in animal models. In addition, 17β-E also regulates male-type sexual and agg...

Certain aspects of social behavior help animals make adaptive decisions during encounters with other animals. When mice choose to approach another conspecific, the motivation and preference behind the interaction is not well understood. Furthermore, estrogen and oxytocin are known to influence a wide array of social behaviors, including social moti...

17β-Estradiol (E2) regulates the expression of female sexual behavior by acting through estrogen receptor (ER) α and β. Previously, we have shown that ERβ knockout female mice maintain high level of lordosis expression on the day after behavioral estrus when wild-type mice show a clear decline of the behavior, suggesting ERβ may be involved in inhi...

It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep...

We found a novel sexually dimorphic area in the dorsal hypothalamus of mice (hereafter the SDA-DH). The SDA-DH was sandwiched between two known male-biased sexually dimorphic nuclei, the principal nucleus of the bed nucleus of the stria terminalis and the calbindin-sexually dimorphic nucleus, and exhibited a female-biased sex difference in neuronal...

Significance Testosterone stimulation during the pubertal period is necessary for the full expression of male-type social behaviors. However, it is not known whether estrogen receptor (ER) α may be involved in pubertal organizational action of testosterone on the regulation of male-type social behaviors. In this study, we showed that the prepuberta...

Reproduction consists of various physiological events including fertilization, development of sexual characteristics, social behavior, maturation, and aging. Reproductive functions are ultimately regulated by the hypothalamus-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) is a pivotal hypothalamic neuropeptide that regulates ve...

Testosterone, after being converted to estradiol in the brain, acts on estrogen receptors (ERα and ERβ) and controls the expression of male-type social behavior. Previous studies in male mice have revealed that ERα expressed in the medial preoptic area (MPOA) and medial amygdala (MeA) are differently involved in the regulation of sexual and aggress...

This study investigated the role of estrogen receptors alpha (ERα) in the ventromedial nucleus of the hypothalamus (VMN),the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behavior in female rats. This was done in two sets of experiments, with the VMN and POA investigated in the first s...

Expression of social behaviors is regulated by various neuroendocrine and neurochemical factors. Among them, estradiol is known to have a profound influence on female sexual behavior as well as various types of social interactive behaviors, through its binding to two types of estrogen receptors, ERα or ERβ. Since male gonadal hormone, testosterone,...

Sex steroid action is critical to form sexually dimorphic nuclei, although it is not fully understood. We previously reported that masculinization of the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is larger and has more neurons in males than in females, involves aromatized testosterone that acts via estrogen recepto...

Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER) β plays a pivotal role in the regulation of stres...

Background/aims: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are a...

The opioid peptides, dynorphin (DYN) and enkephalin (L-ENK) are contained in the hippocampal mossy fiber pathway where they modulate synaptic plasticity. In rats, the levels of DYN and L-ENK immunoreactivity (-ir) are increased when estrogen levels are elevated (Torres-Reveron et al., 2008 and 2009). Here, we used quantitative immunocytochemistry t...

In the sexually dimorphic anteroventral periventricular nucleus (AVPV) of the hypothalamus, females have a greater number of tyrosine hydroxylase-immunoreactive (TH-ir) and kisspeptin-immunoreactive (kisspeptin-ir) neurons than males. In this study, we used proteomics analysis and gene-deficient mice to identify proteins that regulate the number of...

Oestrogen receptor (ER)α plays important roles in the development and function of various neuronal systems through activation by its ligands, oestrogens. To visualise ERα-positive neurons, we generated transgenic (tg) mice expressing green fluorescent protein (GFP) under the control of the ERα promoter. In three independent tg lines, GFP-positive n...

Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related n...

Testosterone is known to play an important role in the regulation of male-type sexual and aggressive behavior. As an aromatised metabolite of testosterone, estradiol-induced activation of estrogen receptor α (ERα) may be crucial for the induction of these behaviors in male mice. However, the importance of ERα expressed in different nuclei for this...

Gonadal steroid hormones, androgen and estrogen, regulate the expression of sex-typical behavior through organizational and activational action. To understand the biological basis of animal behavior, particularly social behavior, it is very important to focus on the life-long action of various hormones in the brain. In this article, we first summar...

The medial preoptic area has been shown to be intricately involved in many behaviors, including locomotion, sexual behavior, maternal care, and aggression. The gene encoding estrogen receptor-α (ERα) protein is expressed in preoptic area neurons, and a very dense immunoreactive field of ERα is found in the preoptic region. ERα knockout animals show...

Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the...

MS effects on social investigative behaviors during stimulus exposure. (MOV)

Long-term social preference test (SPT) apparatus. Top view of the long-term social preference test apparatus (AMAZENG TYPE1), which consisted of one large cage connected to two smaller cages by clear acrylic tunnels. At the end of each tunnel, wire mesh prevented physical contact between experimental and stimulus mice except for the tip of their no...

Litter effects on OFT, LDT, and short-term SPT behavioral measurements. (MOV)

Social investigation test of control and MS females tested against unfamiliar male stimuli mice. Control females, but not MS females displayed high levels of social investigation towards the male stimulus-containing cylinder. On the other hand, MS females displayed frequent stretched approaches. Left, control female; right, MS female. (DOC)

Social investigation test (SIT) apparatus. (A) The apparatus (SOSI TYPE1) consisted of a (B) white plastic testing cage and (C) Plexiglas cylinders (Mouse Cylinder SIOT1) used to introduce the stimulus mouse. Near the bottom of the each cylinder are 28 holes that allow the experimental mouse to be exposed to olfactory cues from the stimulus mouse....

Social investigation test of control and MS females tested against unfamiliar female stimuli mice. Control females exhibited high levels of social investigation of female stimulus-containing cylinder, whereas MS females displayed numerous stretched approaches toward the stimulus-containing cylinder and low social investigation. Left, control female...

Ovariectomized females were given an infusion in the medial preoptic area (MPOA) of a viral vector carrying either a shRNA directed against the estrogen receptor α (ERα) or luciferase. The females were subjected to a test for sexual incentive motivation immediately followed by a test for receptivity and proceptive behaviors. Two weeks later they we...

Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning....

Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evi...

The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is a sexually dimorphic nucleus, and the male BNSTp is larger and has more neurons than the female BNSTp. To assess the roles of neuroestrogen synthesized from testicular androgen by brain aromatase in masculinization of the BNSTp, we performed morphometrical analyses of the a...

Clinical evidence suggests that antiestrogens inhibit the development of androgen-insensitive prostate cancer. Here, we show that the estrogen receptor β (ERβ) mediates inhibition by the antiestrogen ICI 182,780 (ICI) and its enhancement by estrogen. ERβ associated with gene promoters through the tumor-suppressing transcription factor KLF5 (Krüppel...

To investigate the effects of early life stress on the development of social behaviors in male mice, we examined behavioral responses toward same sex stimulus mice in the social investigation test and aggressive behaviors in peripubertal male mice exposed to maternal separation (MS) during the first 2 weeks of life. MS suppressed aggressive behavio...

We previously reported that knockout (KO) mice of estrogen receptor (ER) α (αERKO), ERβ (βERKO) and oxytocin (OTKO) show impairments in social recognition (PNAS, 100, 6192-6197, 2003). Based on this behavioral similarity and neuroanatomical evidence, we have hypothesized an estrogen-dependent gene micronet for the regulation of social recognition:...

Stress is one of the important factors to activate the sympathetic nervous system. We recently reported that central administration of corticotropin-releasing factor (CRF), known as a stress-related neuropeptide, increases the expression of both cyclooxygenase (COX) and nitric oxide synthase (NOS) in presympathetic neurons in the paraventricular hy...

The hippocampus has been hypothesized to function as a "spatial" or "cognitive" map, however, the functional cellular organization of the spatial map remains a mystery. The majority of electrophysiological studies, thus far, have supported the view of a random-type organization in the hippocampus. However, using immediate early genes (IEGs) as an i...

Social recognition manifests itself in decreased investigation of a previously encountered individual. Estrogen receptor alpha (ERalpha) knock out mice show deficient social recognition and anxiety. These data show that the ERalpha is involved in these effects, but they do not say anything about the brain sites important for these effects. In this...

Estrogen receptor alpha (ERalpha) typically masculinizes male behavior, while low levels of ERalpha in the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BST) are associated with high levels of male prosocial behavior. In the males of the highly social prairie vole (Microtus ochrogaster), increasing ERalpha in the MeA inhibited...

The display of copulatory behaviors usually requires the presence of a mate and is, therefore, preceded by a search for and approach to a potential partner. The intensity of approach behaviors is determined by a process labeled sexual incentive motivation. Although it is known that female sexual motivation depends on estrogens, their site of action...

Locus coeruleus (LC) is involved in the LHRH regulation by gonadal steroids. We investigated the expression of progesterone and estrogen receptors (PR; ER) in LC neurons of ERalpha (alphaERKO) or ERbeta (betaERKO) knockout mice, and their wild-type (alphaWT and betaWT). Immunocytochemical studies showed that LC expresses PR and both ERs, although E...

The activity-dependent transcription factor zif268 is re-activated in sleep following hippocampal long-term potentiation (LTP). However, the activation of secondary genes, possibly involved in modifying local synaptic strengths and ultimately stabilizing memory traces during sleep, has not yet been studied. Here, we investigated changes in hippocam...

Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (appr...

In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s), the ratio of the various genotypes in the litter....

Studies using estrogen receptor alpha (ERalpha) knock-out mice indicate that ERalpha masculinizes male behavior. Recent studies of ERalpha and male prosocial behavior have shown an inverse relationship between ERalpha expression in regions of the brain that regulate social behavior, including the medial amygdala (MeA), and the expression of male pr...

The developmental process of prolactin (PRL) cells in the fetal pituitary gland was studied in mice. Although PRL cells were hardly detectable in the pituitary gland of intact fetuses, a treatment with 17beta-estradiol (E(2)) in vitro induced a number of PRL cells that varied drastically in number depending on the stage of gestation with a peak at...