BRAIN MECHANISMS OF REPRODUCTIVE BEHAVIOR
Donald Wells Pfaff, Professor And Head Of Laboratory
Rockefeller University, New York, Ny 10065-6399
Grant 5R37HD005751-37 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
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
Keywords: Address; Anti-Sense DNA; Antisense DNA; Antisense Technology; Arm; Arts; Assay; Attention; Back; Behavior; Behavioral; Bioassay; Biodegradable microsphere; Biologic Assays; Biological Assay; Brain; Brain region; Chemotherapy-Hormones/Steroids; Corlutina; Corluvite; Cyclogest; DNA Sequence; DNA, Antisense; Data; Development; Dorsum; Encephalon; Encephalons; Endocrine Gland Secretion; Environment; Equilibrium; Estrogenic Agents; Estrogenic Compounds; Estrogens; Female; Female Health; Gene Expression; Genes; Genetic; Genetic Techniques; Genomics; Gestagenic Agents; Gestagens; Gestation; Gestiron; Gestone; Grant; Head; Hops; Hormonal; Hormones; Humulus; Hypothalamic structure; Hypothalamus; Implant; Individual; Isoforms; Knock-out; Knockout; Knockout Mice; LNA (nucleic acid); Length of Life; Lipo-Lutin; Literature; Locomotion; Longevity; Lordosis; Luteohormone; Lutocyclin; Lutocylin M; Lutogyl; Lutromone; Mammals, Mice; Messenger RNA; Methods; Methods and Techniques; Methods, Other; Mice; Mice, Knock-out; Mice, Knockout; Microbeads; Microinjections; Microspheres; Murine; Mus; Nervous; Nervous System, Brain; Neuroendocrine; Neuroendocrine System; Neurosecretory Systems; Nuclear; Null Mouse; One Step; One-Step dentin bonding system; Partner in relationship; Pattern; Performance; Pregnancy; Preoptic Areas; Progestagenic Agents; Progestasert; Progestational Agents; Progestational Compounds; Progestational Hormones; Progesterone Agents; Progestins; Progestogel; Progestogens; Progestol; Progeston; Prolidon; Proluton; Protein Isoforms; Proteins; RNA, Messenger; Radial; Reagent; Relative; Relative (related person); Reproductive Behavior; Role; Running; SCHED; Schedule; Sex Behavior; Sexual Activity; Sexual Behavior; Site; Social Behavior; Syngesterone; System; System, LOINC Axis 4; Technics, Genetic; Techniques; Testing; Therapeutic Estrogen; Therapeutic Hormone; Therapeutic Progestin; Time; Upper arm; Utrogestan; Viral; Viral Vector; Women`s Health; Work; approach behavior; balance; balance function; base; experiment; experimental research; experimental study; gene product; hypothalamic; knock-down; life span; lifespan; locked nucleic acid; mRNA; male; mate; neural; new approaches; novel; novel approaches; novel strategies; novel strategy; preoptic region; relating to nervous system; research study; response; sex activity; social role; sociobehavior; sociobehavioral; tool
Project start date: 1978-05-01
Project end date: 2013-03-31
Budget start date: 1-APR-2010
Budget end date: 31-MAR-2011
5R37HD005751-37 (2010): $376448
Sponsored Links Excellgen http://Excellgen.com
BRAIN MECHANISMS OF REPRODUCTIVE BEHAVIOR
Donald Wells Pfaff, Professor And Head Of Laboratory
Rockefeller University, New York, Ny 10065-6399
Grant 5R37HD005751-36 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
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
Keywords: Address; Anti-Sense DNA; Antisense DNA; Antisense Technology; Arm; Arts; Assay; Attention; Back; Behavior; Behavioral; Bioassay; Biodegradable microsphere; Biologic Assays; Biological Assay; Brain; Brain region; Chemotherapy-Hormones/Steroids; Corlutina; Corluvite; Cyclogest; DNA Sequence; DNA, Antisense; Data; Development; Dorsum; Encephalon; Encephalons; Endocrine Gland Secretion; Environment; Equilibrium; Estrogenic Agents; Estrogenic Compounds; Estrogens; Female; Female Health; Gene Expression; Genes; Genetic; Genetic Techniques; Genomics; Gestagenic Agents; Gestagens; Gestation; Gestiron; Gestone; Grant; Head; Hops; Hormonal; Hormones; Humulus; Hypothalamic structure; Hypothalamus; Implant; Individual; Isoforms; Knock-out; Knockout; Knockout Mice; LNA (nucleic acid); Length of Life; Lipo-Lutin; Literature; Locomotion; Longevity; Lordosis; Luteohormone; Lutocyclin; Lutocylin M; Lutogyl; Lutromone; Mammals, Mice; Messenger RNA; Methods; Methods and Techniques; Methods, Other; Mice; Mice, Knock-out; Mice, Knockout; Microbeads; Microinjections; Microspheres; Murine; Mus; Nervous; Nervous System, Brain; Neuroendocrine; Neuroendocrine System; Neurosecretory Systems; Nuclear; Null Mouse; One Step; One-Step dentin bonding system; Partner in relationship; Pattern; Performance; Pregnancy; Preoptic Areas; Progestagenic Agents; Progestasert; Progestational Agents; Progestational Compounds; Progestational Hormones; Progesterone Agents; Progestins; Progestogel; Progestogens; Progestol; Progeston; Prolidon; Proluton; Protein Isoforms; Proteins; RNA, Messenger; Radial; Reagent; Relative; Relative (related person); Reproductive Behavior; Role; Running; SCHED; Schedule; Sex Behavior; Sexual Activity; Sexual Behavior; Site; Social Behavior; Syngesterone; System; System, LOINC Axis 4; Technics, Genetic; Techniques; Testing; Therapeutic Estrogen; Therapeutic Hormone; Therapeutic Progestin; Time; Upper arm; Utrogestan; Viral; Viral Vector; Women`s Health; Work; approach behavior; balance; balance function; base; experiment; experimental research; experimental study; gene product; hypothalamic; knock-down; life span; lifespan; locked nucleic acid; mRNA; male; mate; neural; new approaches; novel; novel approaches; novel strategies; novel strategy; preoptic region; relating to nervous system; research study; response; sex activity; social role; sociobehavior; sociobehavioral; tool
Project start date: 1978-05-01
Project end date: 2013-03-31
Budget start date: 1-APR-2009
Budget end date: 31-MAR-2010
5R37HD005751-36 (2009): $380250
Grants awarded to Donald Wells Pfaff
BRAIN MECHANISMS OF REPRODUCTIVE BEHAVIOR
Donald Wells Pfaff, Professor And Head Of Laboratory
Rockefeller University, New York, Ny 10065-6399
Grant 3R37HD005751-36S1 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
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
Keywords: Address; Anti-Sense DNA; Antisense DNA; Antisense Technology; Arm; Arts; Assay; Attention; Back; Behavior; Behavioral; Bioassay; Biodegradable microsphere; Biologic Assays; Biological Assay; Brain; Brain region; Chemotherapy-Hormones/Steroids; Corlutina; Corluvite; Cyclogest; DNA Sequence; DNA, Antisense; Data; Development; Dorsum; Encephalon; Encephalons; Endocrine Gland Secretion; Environment; Equilibrium; Estrogenic Agents; Estrogenic Compounds; Estrogens; Female; Female Health; Gene Expression; Genes; Genetic; Genetic Techniques; Genomics; Gestagenic Agents; Gestagens; Gestation; Gestiron; Gestone; Grant; Head; Hops; Hormonal; Hormones; Humulus; Hypothalamic structure; Hypothalamus; Implant; Individual; Isoforms; Knock-out; Knockout; Knockout Mice; LNA (nucleic acid); Length of Life; Lipo-Lutin; Literature; Locomotion; Longevity; Lordosis; Luteohormone; Lutocyclin; Lutocylin M; Lutogyl; Lutromone; Mammals, Mice; Messenger RNA; Methods; Methods and Techniques; Methods, Other; Mice; Mice, Knock-out; Mice, Knockout; Microbeads; Microinjections; Microspheres; Murine; Mus; Nervous; Nervous System, Brain; Neuroendocrine; Neuroendocrine System; Neurosecretory Systems; Nuclear; Null Mouse; One Step; One-Step dentin bonding system; Partner in relationship; Pattern; Performance; Pregnancy; Preoptic Areas; Progestagenic Agents; Progestasert; Progestational Agents; Progestational Compounds; Progestational Hormones; Progesterone Agents; Progestins; Progestogel; Progestogens; Progestol; Progeston; Prolidon; Proluton; Protein Isoforms; Proteins; RNA, Messenger; Radial; Reagent; Relative; Relative (related person); Reproductive Behavior; Role; Running; SCHED; Schedule; Sex Behavior; Sexual Activity; Sexual Behavior; Site; Social Behavior; Syngesterone; System; System, LOINC Axis 4; Technics, Genetic; Techniques; Testing; Therapeutic Estrogen; Therapeutic Hormone; Therapeutic Progestin; Time; Upper arm; Utrogestan; Viral; Viral Vector; Women`s Health; Work; approach behavior; balance; balance function; base; experiment; experimental research; experimental study; gene product; hypothalamic; knock-down; life span; lifespan; locked nucleic acid; mRNA; male; mate; neural; new approaches; novel; novel approaches; novel strategies; novel strategy; preoptic region; relating to nervous system; research study; response; sex activity; social role; sociobehavior; sociobehavioral; tool
Project start date: 2009-09-30
Project end date: 2010-09-29
Budget start date: 30-SEP-2009
Budget end date: 29-SEP-2010
3R37HD005751-36S1 (2009): $111342
GENES INFLUENCING SOCIAL BEHAVIORS
Donald Wells Pfaff, Professor And Head Of Laboratory
Rockefeller University, New York, Ny 10065-6399
Grant 3R01MH038273-23S1 from National Institute Of Mental Health
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
Keywords: (17Beta)-17-hydroxyandrost-4-en-3-one; 17-beta-Hydroxy-4-Androsten-3-one; 3-(2-Aminoethyl)-1H-indol-5-ol; 5-HT; 5-Hydroxytryptamine; 5HT; Active Follow-up; Address; Affect; Aggression; Aggressive behavior; Agonist; Amygdala; Amygdaloid Body; Amygdaloid Nucleus; Amygdaloid structure; Androst-4-en-17beta-ol-3-one; Androst-4-en-3-one, 17-(1-oxopropoxy)-(17-beta)-; Animals; Anti-Sense DNA; Antidiuretic Hormone; Antidiuretic Hormones; Antisense DNA; Anxiety; Area; Argipressin; Autism; Autism, Early Infantile; Autism, Infantile; Autistic Disorder; Behavior; Behavioral; Behavioral Assay; Binding; Binding (Molecular Function); Biodegradable microsphere; Brain; Caring; Cell Communication and Signaling; Cell Nucleus; Cell Signaling; Chemotherapy-Hormones/Steroids; Conflict; Conflict (Psychology); Confusion; Confusional State; Crossing Over; Crossing Over, Genetic; DNA, Antisense; DRN; Data; Delta4-androsten-17beta-ol-3-one; Depression, Postpartum; Disease; Disorder; Dorsal; Encephalon; Encephalons; Endocrine Gland Secretion; Enteramine; Environment; Estrogenic Agents; Estrogenic Compounds; Estrogens; Experimental Designs; FLR; Failure (biologic function); Fear; Female; Follow-Up Studies; Followup Studies; Fostering; Fright; Gender; Gene Expression; Genes; Genetic; Genetic Crossing Over; Genomics; Gestation; Hippophaine; Hormonal; Hormones; Intracellular Communication and Signaling; Kanner`s Syndrome; Knock-out; Knockout; Knockout Mice; Knowledge; LNA (nucleic acid); Laboratories; Lactation; Letters; Life; Literature; Logic; Mammals, Mice; Maternal Behavior; Measures; Mental Confusion; Messenger RNA; Methods and Techniques; Methods, Other; Mice; Mice, Knock-out; Mice, Knockout; Microinjections; Molecular; Molecular Interaction; Molecular Target; Motivation; Murine; Mus; Nerve Cells; Nerve Unit; Nervous; Nervous System, Brain; Neural Cell; Neurobiology; Neurocyte; Neuroendocrinology; Neurons; Neuropeptides; Nucleus; Null Mouse; OXT; Ocytocin; Oligo; Oligonucleotides; Oxytocin; Oxytocin Receptor; Pattern; Pharmacology; Phenotype; Pheromone; Post-Natal Depression; Post-Partum Depression; Postnatal Depression; Postpartum Depression; Pregnancy; Preoptic Areas; Preparation; Progress Reports; RNA, Messenger; Reagent; Receptor Gene; Receptor Protein; Recombinant Oxytocin; Regulation; Reports, Progress; Reproduction; Schizophrenia; Schizophrenic Disorders; Serotonin; Signal Transduction; Signal Transduction Systems; Signaling; Site; Social Behavior; System; System, LOINC Axis 4; Techniques; Testing; Testosterone; Testosterone Propionate; Therapeutic Estrogen; Therapeutic Hormone; Therapeutic Testosterone; Thinking; Thinking, function; Time; Trans-Testosterone; Universities; Variant; Variation; Vasopressin, 8-L-arginine-; Vasopressin, Arginine; Vasopressin-Neurophysin II-Copeptin; Vasopressins; Viral Vector; Work; Writing; affiliative behavior; amygdaloid nuclear complex; base; beta-Hypophamine; biological signal transduction; dementia praecox; disease/disorder; dorsal raphe nucleus; experiment; experimental research; experimental study; failure; follow-up; high risk; interest; knockout gene; locked nucleic acid; mRNA; maternal aggression; multidisciplinary; neural; neurobiological; neuronal; new approaches; nonsister chromatid exchange; novel; novel approaches; novel strategies; novel strategy; pregnant; preoptic region; receptor; relating to nervous system; research study; response; schizophrenic; social; sociobehavior; sociobehavioral; tool
Project start date: 2010-03-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
3R01MH038273-23S1 (2010): $242589
5R01MH038273-23 (2009): $320485