The Dual Center Model for Regulation of Feeding paraventricular nucleus is a major source of input to the Most neuroscientists have grown up with the classic sympathetic and parasympathetic preganglionic neu-“dual center” model for understanding the role of the rons controlling the gastrointestinal tract, suggesting brain in regulation of feeding (Stellar, 1954). This model that the changes in feeding might be consequent to was derived originally from clinical observations in paautonomic alterations (Saper et al., 1976; Swanson and tients with Frohlich’s syndrome: pituitary tumors associ-Kuypers, 1980; Saper, 1995). To test this hypothesis, ated with excessive subcutaneous fat and hypogo- Opsahl and Powley (1974) and several subsequent nadism (Bramwell, 1888; Frohlich, 1901). Whether this groups examined the effect of severing the abdominal adiposogenital syndrome was due to injury to the pitu- vagus nerve in rats with large lesions of the ventromedial itary gland (as Frohlich concluded at the time) or to the nucleus, finding that subdiaphragmatic vagotomy preoverlying hypothalamus was controversial. Cushing, for vented the hyperphagia and obesity (Inoue and Bray, example, championed the view that Frohlich’s syndrome 1977; Berthoud and Jeanrenaud, 1979; Gold et al., 1980; was due to hypophysial insufficiency (Crowe et al., Bray et al., 1981; Cox and Powley, 1981; Sclafani et al., 1910). In 1912, Aschner demonstrated in dogs that mere 1981). At the same time, several groups pointed out that removal of the pituitary gland without damage to the over- the lateral hypothalamic lesions that cause hypophagia lying hypothalamus did not result in obesity (Aschner, interrupt the ascending nigrostriatal bundle, resulting in 1912). a Parkinsonian syndrome and reduction in virtually all The role of the hypothalamus in regulating food intake movement and behavior (see Ungerstedt, 1970; Stricker and body weight was finally established in 1940 with and Zigmond, 1976; Stricker and Verbalis, 1990; Berthe classic experiments of Hetherington and Ranson. nardis and Bellinger, 1996). They used the Horsley–Clarke stereotaxic apparatus to place bilateral electrolytic lesions in the hypothalamus of New Molecular Probes Verify the Presence rats, without disturbing the pituitary gland (Hetherington of Lateral Hypothalamic Phagic Neurons and Ranson, 1940). They summarized these experi- Observations such as these questioned the validity of ments by stating: the dual center model and the role of the lateral hypothalamic area and the ventrobasal hypothalamus in control-A condition of marked adiposity characterized by as ling food intake (Bernardis and Bellinger, 1987, 1996). much as a doubling of body weight and a tremendous Nevertheless, as cell-specific lesion methods emerged, increase of extractable body lipids has been pro- they refocused attention on the ventromedial and lateral duced in rats by the placing of electrolytic lesions in hypothalamic syndromes. Lateral hypothalamic lesions produced by kainic acid resulted in hypophagia, even