Genes Influencing Social Behaviors
Donald Wells Pfaff, Professor And Head
Neurobiology & Behavior Labrockefeller University
Grant 5R01MH038273-23 from National Institute Of Mental Health IRG: NNB
Abstract: A classical view claims that oxytocin (OT) fosters affiliative behaviors and arginine vasopressin (VP) enhances aggression. But a lot of data conflict with this. The confusion is not due purely to neuroanatomical details, or gender or species. I will use two novel approaches to compare OT and VP responsive systems (I.) Using molecular tools and some new behavioral thinking; and (II.) Using estrogens (E) as biologically relevant probes. In order to take maximal advantage of genetic knowledge and preliminary evidence we will use female mice. Specifically Aim I. I will perturb OT gene expression and OT receptors using gene knockouts - with all interesting results followed up by a novel antisense DNA technique - and measure an interesting behavior maternal aggression (as part of reproduction), compared to an ´affiliative behavior´, maternal care compared to testosterone-facilitated aggression. (I have already shown that seminatural environment living helps to reveal hitherto unrealized behavioral phenotypes.) Aim II. Estrogenic regulations of these systems offer the opportunity to probe with novel E-related molecular tools. Will ER gene knockout mice, antisense oligos, and selective agonists and antagonists change the three behaviors above in the predicted directions? Aim III. Will verify major discoveries of this project in normal pregnant and lactating mice. In all Aims, important targets for molecular manipulations will be in the amygdala The basolateral nuclei are involved in fear; the central nucleus in anxiety; and the mediocortical region in signaling by pheromones. All of these functions could influence the three behaviors measured in this project. Also important The dorsolateral preoptic area for maternal behavior, and the dorsal raphe for serotonin and aggression. This project uses the multidisciplinary capacity of my laboratory and the Rockefeller University campus, and is written in an "if/then" style to show how we will maximize the impact of 5 years of work. These experiments will increase our understanding of two extremely important transcriptional systems, OT and VP, with widespread projections and significant autonomic and behavioral effects. Impact OT may be involved in postpartum depression. OT systems certainly facilitate social recognition, disorders of which are prominent in autism and in schizophrenia
Project start date: 1989-02-01
Project end date: 2010-05-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Donald Wells Pfaff
Brain Mechanisms Of Reproductive Behavior
Donald Wells Pfaff, Professor And Head
Neurobiology & Behavior Labrockefeller University
Grant 5R37HD005751-36 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development IRG: NSS
Abstract: Great progress has been made in the analysis of hormonal, neural and genetic mechanisms underlying a simple sex behavior, lordosis. Now, it would be exciting to understand the flow of behaviors leading up to mating. Also, to explore the behavioral dispositions underlying these proceptive behaviors by the female. We have discovered active approach and pacing behaviors, previously thought to be absent, in female mice. New experiments with mice will allow for ´state of the art´ genetic elucidation. (Aim I.) To finish carefully characterizing these locomotor, approach, proceptive and pacing behaviors. Included are quantitative analyses in seminatural environments which encourage a full range of social behaviors by the female, in their natural form. We have already discovered Direct Approaches, Head Turns, Hop-and-Stops, and Dart/Return Pacing responses. This is almost finished and will not take long. (Aim I1.) We will determine their hormonal facilitation. For the first time in mice, the relative importance of estrogens (E), progestins (P) and their combination will be explored. New data comparing the roles of P and the gene for PRs in small shoebox cages compared to a seminatural environment already show us the importance of context in discerning hormone/gene/behavior causal relations. (Aim III) We will discover their CNS sites of hormone action and genetic influences. For the genetics, primarily, a novel antisense technology will be used. Both hormonal experiments and antisense DNA experiments will include the use of a new ´microsphere´ delivery system for hormones and for antisense DNA reagents. The antisense and microsphere techniques, well documented elsewhere, can be applied for the first time to the mouse CNS. Using female mice allows us to apply novel genetic tools. Analyzing the entire sequence of behaviors preceding lordosis, we can address scientifically exciting questions about reproductive behaviors which are not simple and which are biologically important. These behaviors bring together, at the right time, conspecifics who are competent to reproduce. Further, increasing attention to broader, hormone-dependent behavioral dispositions brings us one step closer to issues important for women´s health
Project start date: 1978-05-01
Project end date: 2013-03-31
3R37HD005751-36S1 (2009): $111342