Richmond Thompson, PhD - US grants

There are two closely related peptide hormones called arginine vasotocin
(AVT) and arginine vasopressin (AVP) that have been implicated in several
vertebrates as modulators of social behavior, including courtship, pair-bonding,
parenting, and aggression. The mechanisms by which these molecules act in
the brain to produce these behavioral effects remain unclear, but their
widespread distribution suggests they are evolutionarily conserved. It has been
suggested that AVT/AVP may affect the processing of species-typical social
releasing stimuli such as courtship calls, visual displays, or chemical signals. It is
important to take a comparative approach to this question, to determine whether
or not AVT/AVP can selectively influence behavioral and brain responses to the
specific releasing stimuli that have evolved in different groups of animals for
social communication. This project is a Small Grant for Exploratory Research to
test this hypothesis directly using goldfish, because the exact chemical stimuli
important for courtship and aggressive communication signals in this species are
uniquely identified and can be delivered quantitatively. The project is exploratory
because it is not yet clear whether AVT will influence social behavior in goldfish,
although AVT effects on social behavior have been shown in other teleost fish,
and some AVT/AVP effects are known for diverse other vertebrates.
Experiments manipulating AVT levels in the brain will measure effects on
courtship and aggressive behaviors in male goldfish during responses to
particular chemosensory social stimuli that release those behaviors.
This is a high-impact/high-risk project because the outcome is not clear, but
the potential impact of success is wide-ranging. If successful, the results will
lead to further studies on social regulatory functions of hormones, will have an
impact beyond behavioral neuroendocrinology to brain neurochemistry, animal
behavior, and evolutionary neuroscience, and could have an impact on
applications in aquaculture and fisheries industries.

DESCRIPTION (provided by applicant): The proposed study will broaden our understanding of how brain neurochemistry affects emotional communication in humans. Specifically, it will determine if arginine-vasopressin (AVP), an endogenous neuropeptide known to influence various social behaviors in non-human vertebrates, affects autonomic and / or somatic responses to emotional facial expressions in humans. This goal will be accomplished by measuring the effects of intranasally administered AVP in post-pubertal men and women on heart rate and skin conductance and on the electromyographic (EMG) responses of multiple facial muscles in response to facial expressions that vary in their emotional content. Preliminary results indicate that AVP selectively increases the EMG responses of the corrugator supercilii that are evoked by emotionally neutral facial expressions to levels typically seen in response to angry facial expressions in control subjects. Because corrugator supercilii activity is associated with the perception of angry / threatening social stimuli and with the generation of facial expressions related to anger towards another individual, this result suggests that AVP may affect agonistic communication processes in humans by biasing individuals to respond to emotionally ambiguous social stimuli as if they were threatening. The present study will extend that finding by determining the time course for this effect, determining if AVP affects multiple facial muscles whose coordinated activity comprises a somatic "signature" associated with the perception of threatening social stimuli, determining if ratings of the perceived sociability of emotional facial stimuli are influenced by AVP administration, and determining if AVP influences on the processing of facial stimuli are present in women as in men. The findings from this research will help elucidate the mechanisms through which this neuropeptide influences social communication in humans, particularly agonistic communication. Such knowledge may ultimately help us better understand and treat mental disorders like depression and autism, which involve, among other things, difficulties processing emotional information related to social communication.

Vasotocin is a chemical produced in the brains of fish, reptiles, amphibians and birds and is very similar to a chemical produced in the brains of mammals, including humans, which is called vasopressin. These related chemicals influence a variety of social behaviors, including courtship, aggression, and pair-bonding in numerous animals, possibly even in humans. However, little is known about how these chemicals act inside of the brain to exert their influences on a variety of behaviors. Goldfish are an ideal species in which to study such processes because they are very social and because the vasotocin systems in their brains are easily manipulated, to reveal important mechanisms for how these chemicals might work. In goldfish, vasotocin inhibits a very basic form of social behavior, approach responses toward other fish. The present project will use behavioral, neuroanatomical and molecular techniques to determine how and where vasotocin acts within the brain to induce such effects and if different levels of sociality are associated with individual differences in these brain systems. It is predicted that vasotocin inhibits social approach behavior in this species by activating brain systems involved in the control of body processes related to emotional fight or flight reactions. Because the brain vasotocin and vasopressin systems that potentially control such processes are similar in many animals, including humans, such findings could implicate mechanisms that may be widespread in the animal kingdom and may even represent one of the original ways through which this chemical affected social behavior in vertebrate animals. Therefore, these studies have the potential to increase our understanding of how the brain systems that control social behavior may have evolve, as well as of how specific neurochemical processes influence social behavior in modern species. Undergraduate students, many whom are senior honor's students, will play an important role in the implementation of studies addressing these specific goals.

Steroid hormones exert profound effects on social behavior, but those effects are typically slow because steroids activate molecules that turn genes on and off, and changes in gene activity take a long time to produce effects on behavior. However, it has recently been shown that steroids can also affect behavior through more rapid mechanisms that do not depend on interactions with genes. Thompson will test the hypothesis that two sex steroids, testosterone and estradiol, affect reproductive behavior in male goldfish by rapidly changing how goldfish see the world, particularly female sexual stimuli. The proposal outlines a series of behavioral, electrophysiological, and neuroanatomical experiments that will also determine the kinds of molecules in the brain that these steroid hormones act upon to produce behavioral effects. Additionally, the project will identify where within the brain hormones produce those effects. Together, these experiments will increase our understanding of the fundamental cellular mechanisms through which steroid hormones affect behavior, particularly those related to reproduction. The principal investigator will perform many experiments related to this grant in an upper level laboratory course at Bowdoin College, providing meaningful research experiences to undergraduate students. Dr. Thompson will also teach a summer neuroscience outreach program at Bowdoin College for teams of high school teachers and their students. This will be followed by his students setting up presentations in the classes of teachers who have participated.

DESCRIPTION (provided by applicant): Arginine vasopressin (AVP) and related peptides have profound influences on social behaviors in vertebrates, particularly on emotional aggressive and affiliative interactions between individuals. Although we have recently shown that AVP can promote antisocial responses towards same-sex social stimuli in men and affiliative responses towards same-sex social stimuli in women, we do not yet know if there are sexually dimorphic AVP circuits that promote different social responses in the sexes, or rather if AVP's antisocial and affiliative effects depend on social context, specifically whether the social stimulus is male or female. The first aim of this application is therefore to measure the effects of intranasal AVP on emotional responses to same and other sex faces in men and women to see if AVP produces antisocial effects towards males and affiliative effects towards females, or rather if AVP uniformly promotes antisocial responses in males and affiliative responses in females. This will be done by measuring the effects of AVP on somatic responses associated with anger and threat (contractions of the corrugator supercilii) and with affiliation (contractions of the zygomaticus major, which control smiling) when subjects view the faces of same and other sex individuals, and by measuring the effects of AVP on perceptual responses to those faces, particularly on ratings of friendliness / approachability. We will also determine the dose-responsiveness for these effects, and determine if the magnitude of AVP's antisocial and/or affiliative effects depend on background genotype, particularly on allelic variations in the polymorphic RS3 promoter region of the AVP V1a receptor gene. Finally, we will identify regions in the brain where responses to those social stimuli change as a function of AVP administration. Together, these studies will elucidate the context and gender specificity of AVP's effects on emotional social communication in humans, as well as the molecular and neuroanatomical mechanisms associated with those effects. Ultimately, these studies will not only increase our understanding of the neurochemical mechanisms associated with normal social / emotional regulation in humans, but also our understanding of how dysfunctions within one of those systems may contribute to disorders characterized by social / emotional disturbances. PUBLIC HEALTH RELEVANCE: By determining if arginine vasopressin (AVP) can influence emotional social communication in men and women, particularly if it promotes antisocial and/or affiliative responses to social stimuli in men and women, the studies associated with this application will ultimately help us better understand and treat individuals with disorders that affect emotional social regulation, most notably those with autism and/or antisocial personality disorder. In fact, these studies could ultimately help develop pharmacological and/or genetic therapies that could help alleviate some of the otherwise intractable symptoms associated with these disorders.