The long-term goal of these experiments is to define the organization of the neural networks responsible for anorexia in rats. In particular, studies will focus on interactions between the telencephalon, and the hypothalamus and hindbrain, since the telencephalon likely plays a critical role in clinically-relevant anorexias. The main hypothesis is that the lateral hypothalamic area and the paraventricular nucleus of the hypothalamus contain neurons that constitute a ?feeding behavior controller?, and are sites where distinct feeding stimuli converge to control the core circuits that drive feeding. The goal is to determine the locations of the points of convergence, and to explore how these are affected during anorexia. Three hypotheses will be addressed by the specific aims. They are: 1) Information encoding nucleus accumbens shell (ACBsh)-muscimol and 2-deoxy-D-glucose-driven feeding converges onto the same neurons in the LHA and PVH; 2) ACBsh-muscimol feeding requires input from either the hindbrain or NPY-Y1 receptor expressing neurons in the mediobasal hypothalamus (MBH) for full expression; 3) projections from either the hindbrain or NPY-Y1 receptor expressing neurons in the MBH to the PVH and LHA are required for water-back feeding. Experiments will use two approaches: first, a fine-grained analysis of the structure of ACBsh-muscimol and 2-deoxy-D-glucose-driven feeding in control and anorexic animals; second, a novel immunocytochemical coincidence detection (based on the differential accumulation and degradation rates of Fos and phosphorylated-ERK/2) that reveals neurons that are activated by two convergent feeding stimuli. Circuits will be manipulated using saporin-based immunotoxic lesions that destroy either the ascending catecholaminergic neurons from the hindbrain, or NPY-Y1 receptor expressing neurons in the MBH. Importantly, the types of feeding that are impacted these two techniques are clearly dissociable. Collectively, the experiments in this project are designed to make major contributions towards elucidating the organization and function of the neural circuits responsible for anorexia in animals in a way that will ultimately help to clarify the neural substrates of clinically important anorexias.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH066168-06A1
Application #
7464513
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Vicentic, Aleksandra
Project Start
2002-08-06
Project End
2013-03-31
Budget Start
2008-06-01
Budget End
2009-03-31
Support Year
6
Fiscal Year
2008
Total Cost
$366,750
Indirect Cost
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Boyle, Christina N; Lorenzen, Sarah M; Compton, Douglas et al. (2012) Dehydration-anorexia derives from a reduction in meal size, but not meal number. Physiol Behav 105:305-14
Watts, Alan G; Boyle, Christina N (2010) The functional architecture of dehydration-anorexia. Physiol Behav 100:472-7
Salter-Venzon, Dawna; Watts, Alan G (2009) Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats. Am J Physiol Regul Integr Comp Physiol 297:R1813-21
Salter-Venzon, Dawna; Watts, Alan G (2008) The role of hypothalamic ingestive behavior controllers in generating dehydration anorexia: a Fos mapping study. Am J Physiol Regul Integr Comp Physiol 295:R1009-19
Watts, Alan G; Salter, Dawna S; Neuner, Christina M (2007) Neural network interactions and ingestive behavior control during anorexia. Physiol Behav 91:389-96
Watts, Alan G; Sanchez-Watts, Graciela (2007) Rapid and preferential activation of Fos protein in hypocretin/orexin neurons following the reversal of dehydration-anorexia. J Comp Neurol 502:768-82
Watts, Alan G; Khan, Arshad M; Sanchez-Watts, Graciela et al. (2006) Activation in neural networks controlling ingestive behaviors: what does it mean, and how do we map and measure it? Physiol Behav 89:501-10
Watts, Alan G (2005) Glucocorticoid regulation of peptide genes in neuroendocrine CRH neurons: a complexity beyond negative feedback. Front Neuroendocrinol 26:109-30
Swanson, Larry W; Sanchez-Watts, Graciela; Watts, Alan G (2005) Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone. Neurosci Lett 387:80-4