This application is a request for an Independent Scientist Award (K02) to further the research career development of Dr. Laurence Tecott. Dr. Tecott's long term goal is to apply molecular genetic approaches to determine the contributions of individual serotonin receptor subtypes to the serotonergic regulation of complex behaviors. A major focus of this work will be the development of genetic and behavioral approaches for determining the neural mechanisms through which the serotonin 5-HT2C and 5-HT1A receptor subtypes regulate food intake. Preliminary evidence reveals a dysregulation of feeding in 5-HT2C receptor mutant mice, leading to the development of obesity. Preliminary studies of 5-HT1A receptor mutant mice raise the possibility that these animals have hyperactive brain serotonin systems. The impact of 5-HT2C and 5-HT1A receptors on the neuropsychological processes that regulate feeding will be correlated with their effects on neurotransmitter systems implicated in the regulation of ingestive behavior. An Independent Scientist Award will allow Dr. Tecott to develop new skills and approaches for pursuing his research goals. For example, a major focus of the research plan is the development of ingestive behavior assays for the mouse. These efforts will facilitate the application of transgenic technologies to the study of feeding and enable Dr. Tecott to gain an appreciation of quantitative approaches to the assessment of behavior. Another important goal of the research plan is the development of procedures for generating 5-HT receptor mutations that are restricted to particular brain regions and neurochemically identified cell types. Such approaches will be useful for identifying neural structures through which 5-HT receptors influence complex behaviors. These goals will be pursued with guidance from outstanding collaborators, allowing Dr. Tecott to develop expertise that will complement his existing neuroanatomical and molecular biology skills.
|Goulding, Evan H; Schenk, A Katrin; Juneja, Punita et al. (2008) A robust automated system elucidates mouse home cage behavioral structure. Proc Natl Acad Sci U S A 105:20575-82|
|Tecott, Laurence H (2003) The genes and brains of mice and men. Am J Psychiatry 160:646-56|
|Nonogaki, Katsunori; Abdallah, Luna; Goulding, Evan H et al. (2003) Hyperactivity and reduced energy cost of physical activity in serotonin 5-HT(2C) receptor mutant mice. Diabetes 52:315-20|
|Ruan, Y; Tecott, L; Jiang, M M et al. (2001) Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized. Proc Natl Acad Sci U S A 98:9907-12|
|Tecott, L H; Wehner, J M (2001) Mouse molecular genetic technologies: promise for psychiatric research. Arch Gen Psychiatry 58:995-1004|