Response to social stress: Sensory input, stress response and the neural substrates of reproductive suppression

Social interactions can influence behavior and physiology via several mechanisms. During social stress, subordinate individuals often exhibit behavioral inhibition, and morphological and physiological changes from body appearance to gene expression. In particular, reproduction and stress response are two main foci when considering social regulation among vertebrates. However, it remains unknown what neural mechanisms underlie the social regulation of stress and reproduction and how these are related. In this research, I used an animal model system which has extreme levels of social regulation amongst males, the African cichlid fish Astatotilapia burtoni ( A. burtoni), to ask questions about how the social environment influences behavior and physiology.;In my first experiments, I used a novel paradigm to test the role of vision in social control. Although social interactions typically involve the integration of information from multiple sensory modalities, I wanted to isolate the role of vision. A. burtoni, in which males display plasticity in the reproductive system in response to changes in social status rely extensively on visual communication. A. burtoni males exist in one of two states: territorial (T) males which are brightly colored, reproductively competent and exhibit complex behaviors and non-territorial (NT) males which are camouflage colored, reproductively incompetent, act submissively in the presence of T males, and have higher circulating stress hormone. I showed that A. burtoni respond to visual cues as a key source of social information in establishing a social hierarchy, but that vision alone cannot maintain the suite of physiological changes in a subordinate animal.;During the one week test periods, when dominant males were exposed to larger conspecifics without physical contact, their behavior was that characteristic of a subdominant animal. However, their plasma androgen level was lower and related to the decreased aggressive behavior only on the first day. After three days of visual stimulation, viewers increased the total expression level of the reproductive or stress-related genes for against status loss and copied the visual stress. Thus, the visual cues facilitate social suppression in dominant males, but complete drop in social status may require the integration of other sensory modalities.;To understand the neural basis of the stress response, I analyzed the stress-related gene family, corticotropin-releasing factor (CRF), named for its essential role in mediating the release of the stress hormone, cortisol. CRF also influences numerous other physiological processes via two distinct CRF receptors (CRF-Rs), and is co-regulated by a CRF binding protein (CRFBP). During long term social stress, social information initially changes the basal cortisol level set point in the dorsal telencephalon via decreased cortisol sensitivity. Following cortisol elevation, the down regulation of the CRF systems in hypothalamic pituitary interrenal (HPI) axis is due to the cortisol feedback and cortical inhibition from the ventral telencephalon via elevated cortisol sensitivity. Subordinate behaviors are also related to the activation of arginine vasotocin (AVT) and CRF which helps explain the effect of aggression suppressing behavior and anxious behavior. Interestingly, several studies have shown that CRF and AVT play a role in spatial memory for territory and social behavior across many vertebrate species.;It is well known that social stress influences reproduction. Gonadotropin-releasing hormone (GnRH) was originally identified because of its essential role in regulating reproduction in all vertebrates. In A. burtoni, I have found that CRF peptides and both the CRF-Rs were co-localized with GnRH1 neurons in hypothalamus, implying a direct synaptic pathway between neurons regulating both stress and reproduction. Moreover, the activation of GnRH reproduction is not limited by the androgen feedback or cortical control. The GnRH neurons in the preoptic area were considered to be the site of the social set-point for reproduction under social stress. Thus, the downstream reactions of GnRH system via GnRH receptors play a main role in the social control of reproduction.;Multiple GnRH receptors (GnRH-Rs) regulate endocrine functions and neural transmission in vertebrates. Our study provides a rational nomenclature for GnRH receptors based on phylogenetic and structural analyses of coding sequences. In A. burtoni, GnRH-R1 is up-regulated in the pituitaries of territorial males and I have shown that it is co-localized with pituitary gonadotropes, indicating its function in controlling reproduction. GnRH-R2 in A. burtoni is widely expressed and especially co-localized with all three types of GnRH neurons. Thus, these two receptors suggest that there is a sub-functionalization of these receptor types. Based on their localization, GnRH, in addition to its primary role in regulating reproduction, also can act in autoregulation of GnRH expression, cognition, sensory and motor behavior.