Donald Wells Pfaff - US grants
Affiliations: | Rockefeller University, New York, NY, United States |
Website:
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Donald Wells Pfaff is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
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1985 — 2012 | Pfaff, Donald Wells | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Brain Mechanisms of Reproductive Behavior @ Rockefeller University |
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1986 | Pfaff, Donald Wells | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Control of Postural Changes in Emotional Behavior @ Rockefeller University The proposed research plan represents a series of multidisciplinary investigations which will characterize the motor-related output from limbic forebrain and brainstem regions to the back axial muscles during the performance of a hormone-dependent behavior in chronic preparations. The lordosis reflex of the rat will serve as the model behavior. Neural stimulation, endocrine dose-response, and electromyographic methodologies are employed in order to study limbic and hormonal influences on the electromyographic records of lumbar musculature. Temporal comparisons will be made between 1) the EMG profiles of the motor output with and without neural stimulation, 2) postural data obtained from a length gauge fastened to the vertebral column, and 3) the onset and duration of the somatosensory stimulation which elicits motor output. These comparisons will provide information concerning 1) the influences of limbic forebrain and brainstem stimulation on spinal motor mechanisms which effect the behavioral output, 2) a correlation of muscle activity with the characteristic vertebral dorsiflexion of lordosis, 3) duration of muscle activity during the behavior, 4) the onset latencies of activity of the muscles involved with respect to the onset of cutaneous stimulation, and 5) the effects of estrogen and progesterone administration on the EMG response. Acute studies of the influences of limbic forebrain regions on the axial musculature will complement existing data on the influences from the pontomedullary reticular formation. The participation of limbic structures in lordosis behavior, the endocrine dependence of the behavior, the involvement of postural muscles which have been implicated in tension, stress, and lower lumbar back pain, the quantifiability of the data base, and the proven methodology all contribute to the justification that this systems serves as a viable model of emotional behavior. The proposed research plan not only serves as a logical next step in the analysis of this sterotyped behavior, it also represents the initial phase of this investigator's goal study the limbic control of emotional responses. |
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1986 — 1987 | Pfaff, Donald Wells | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Brain Mechanisms of Reproductive Behavior in Rats @ Rockefeller University Mechanisms of female reproductive behavior, especially regarding hormone effects on the lordosis response, are among the best worked out in mammalian brain. Knowledge of its neural circuitry provides a platform for looking with increased detail at cellular mechanisms for this behavior, which is required for reproduction because it allows fertilization by the male. Following extensive analyses of cellular changes following estradiol (E), it now is easier to study cellular changes which underline progesterone (p)-facilitated behavior. Because effects of progesterone on lordosis require new protein synthesis, classical progestin receptors may play a role. We will use steroid autoradiography to look at receptor/behavior correlations as a function of estrogen dose and anti-progestin dose. What proteins do behaviorally important progestin-receiving cells produce? We will use our technique of combining immunocytochemistry with steroid autoradiography to colocalize nuclear progestin receptors and each of several behaviorally relevant neural proteins. Where do progesterone-receiving cells send their axons? We will combine retrograde neuroanatomical techniques with steroid autoradiography in the same tissue to see if progestin-sensitive cells send axons to certain terminal zones, each implicated in lordosis behavior. In vitro single unit electrophysiology is a chemically clean method of investigating hormone effects on hypothalamic neurons. We will look for electrophysiological/behavioral correlations by giving different E or E+P doses in vivo, testing for lordosis, and studying ventromedial hypothalamic single unit responses to behaviorally active peptides and transmitters. Ultrastructural effects of hormones give clues to guide physiological and behavioral experiments. We will use electron microscopy to look at effects of estrogens and progestins on hypothalamic neurons under conditions which allow morphological/behavioral correlations across hormone treatment durations or amounts of receptor site occupation. Hypothalamic neuron axonal terminals in other brain regions will also be examined. We have developed the application of in situ hybridization techniques to brain tissue, for using labeled cDNA to detect specific messenger RNA in individual cell groups. We will use this technique to study hormone effects on ribosomal RNA and messenger RNA levels for LHRH and proenkephalin. |
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1989 — 1994 | Pfaff, Donald Wells | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Reticulospinal &Vestibulospinal Control of Back Muscles @ Rockefeller University The descending systems comprised of medullary reticulospinal and lateral vestibulo-spinal neurons have been shown to be responsible for facilitating the execution of a mammalian behavior which has been proven to be unusually accessible to cellular and molecular analysis: the estrogen-progestin dependent reproductive behavior, lordosis. Contraction of the deep back muscles to an extent seen in no other behavior, upon somatosensory stimulation on specific regions of skin, is the neuromuscular basis of lordosis. The studies proposed here logically extend previous electrophysiological and behavioral work in our lab. I. Having already established reticulospinal and lateral vestibulospinal control over the deep back muscles lateral longissimus, medial longissimus and transverso-spinalis, we will determine the sensory ascending and brainstem descending neurons which project to the reticulospinal and vestibulospinal neuronal groups responsible. Using microstimulation with currents of 30mualpha or less, we will determine effective sites for the activation of deep back muscles, and use a low- diffusion method of application of retro-grade tracers developed in our lab to see which neurons are projecting to these sites. II. Since damage to the ventromedial nucleus of the hypothalamus can reduce lordosis behavior, we will use large ventromedial hypothalamic lesions (electrolytic or by excitotoxin microinjection) and electrical stimulation, as well as control lesions and stimulation, to discover some of the ways in which medial hypothalamic neurons can influence the ability of reticulospinal and vestibulospinal neurons to facilitate, in turn, deep back muscle motoneurons. Here, and throughout this project, we will use electromyographic (EMG) recording to advantage: it is a productive approach to measuring the output of the motoneuronal pools for deep back muscles. III. Since several hypothalamic neuropeptides have already been characterized with respect to their effects on lordosis behavior, it will be interesting to study their ability to influence the activation of deep back muscle motoneurons by reticulospinal or vestibulospinal neurons. For example, the decapeptide LHRH, known to facilitate reproductive behavior, can be contrasted to beta-endorphin, which decrease lordosis. Work with chronically prepared rats, throughout, will allow comparisons between electromyographic and behavioral observations, while larger numbers of parametric studies can be done efficiently in urethane- anesthetized animals. in the freely moving animals, comparisons of EMG activation across a variety of behavioral situations will reveal those patterns of activity which are specific to the extremely dorsiflexed posture of lordosis. Traditionally in neurobiology, it has been difficult to follow the mechanisms by which forebrain neurons could transmit signals through the brainstem reticular formation, to influence behaviors which are executed through motoneurons located in the spinal cord. These experiments extend our approach to discovering how hypothalamic neurons might influence one, concrete hormone-dependent reproductive behavior. |
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1995 — 2004 | Pfaff, Donald Wells | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Genes Controlling Lordosis Behavior @ Rockefeller University DESCRIPTION: This is a renewal of a project in its ninth year. The goal of this research is to understand the basic working circuit for producing lordosis behavior. The PI's previous work has yielded valuable information on the neural circuitry involved in controlling lordosis. The current work will extend this to an analysis of the molecular mechanisms controlling this behavioral response. The PI will focus this research on the role of oxytocin in mediating the lordosis response because a) it is a behaviorally relevant gene, b) oxytocin is found in brain areas shown to be part of the lordosis circuitry, and b) the genes for both the peptide (oxytocin) and its receptor are known. There are essentially two specific aims. The first is to examine the effectiveness of blocking the oxytocin gene on lordosis and to characterize this effect. The second aim is to do basically the same thing for the oxytocin receptor gene. The PI has preliminary data which provide support for the rationale and feasibility of the proposed experiments. The PI has shown, for example, that the facilitatory effect of oxytocin on lordosis is situated in the VMN, a site containing oxytocin receptors. He has also demonstrated that the excitatory action of oxytocin is mediated via oxytocin receptors. Using antisense oligo's for the oxytocin receptor the PI has found that lordosis is blocked when females are given estradiol (but not estrogen followed by progesterone). Finally, to show that the antisense technology works, he provides data from his laboratory showing that antisense oligo s for PR s reduce lordosis, and that PRir is reduced in VMN. |
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2005 — 2010 | Pfaff, Donald Wells | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Genes Influencing Social Behaviors @ Rockefeller University DESCRIPTION (provided by applicant): 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. |
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