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The Journal of Neuroscience, November 24, 2004, 24(47):10603-10615; doi:10.1523/JNEUROSCI.3390-04.2004

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Behavioral/Systems/Cognitive
Lateral Hypothalamic Signaling Mechanisms Underlying Feeding Stimulation: Differential Contributions of Src Family Tyrosine Kinases to Feeding Triggered Either by NMDA Injection or by Food Deprivation

Arshad M. Khan,^1,3 Herman H. Cheung,⁴ Elizabeth R. Gillard,^1,2 Jennifer A. Palarca,¹ Derek S. Welsbie,³ James W. Gurd,⁴ and B. Glenn Stanley^1,2

Departments of ¹Cell Biology and Neuroscience and ²Psychology and ³Division of Biomedical Sciences, University of California, Riverside, California 92521, and ⁴Centre for the Neurobiology of Stress, Division of Life Sciences, University of Toronto at Scarborough, West Hill, Ontario M1C 1A4, Canada

In rats, feeding can be triggered experimentally using many approaches. Included among these are (1) food deprivation and (2) acute microinjection of the neurotransmitter L-glutamate (Glu) or its receptor agonist NMDA into the lateral hypothalamic area (LHA). Under both paradigms, the NMDA receptor (NMDA-R) within the LHA appears critically involved in transferring signals encoded by Glu to stimulate feeding. However, the intracellular mechanisms underlying this signal transfer are unknown. Because protein-tyrosine kinases (PTKs) participate in NMDA-R signaling mechanisms, we determined PTK involvement in LHA mechanisms underlying both types of feeding stimulation through food intake and biochemical measurements. LHA injections of PTK inhibitors significantly suppressed feeding elicited by LHA NMDA injection (up to 69%) but only mildly suppressed deprivation feeding (24%), suggesting that PTKs may be less critical for signals underlying this feeding behavior. Conversely, food deprivation but not NMDA injection produced marked increases in apparent activity for Src PTKs and in the expression of Pyk2, an Src-activating PTK. When considered together, the behavioral and biochemical results demonstrate that, although it is easier to suppress NMDA-elicited feeding by PTK inhibitors, food deprivation readily drives PTK activity in vivo. The latter result may reflect greater PTK recruitment by neurotransmitter receptors, distinct from the NMDA-R, that are activated during deprivation-elicited but not NMDA-elicited feeding. These results also demonstrate how the use of only one feeding stimulation paradigm may fail to reveal the true contributions of signaling molecules to pathways underlying feeding behavior in vivo.

Key words: eating; feeding; lateral hypothalamic area; glutamate; NMDA; NR2A; NR2B; Src; Pyk2; tyrosine phosphorylation; signal transduction

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Received Aug 18, 2004; revised October 6, 2004; accepted October 6, 2004.

This article has been cited by other articles:

				H. Huang and A. N. van den Pol Rapid Direct Excitation and Long-Lasting Enhancement of NMDA Response by Group I Metabotropic Glutamate Receptor Activation of Hypothalamic Melanin-Concentrating Hormone Neurons J. Neurosci., October 24, 2007; 27(43): 11560 - 11572. [Abstract] [Full Text] [PDF]

				A. M. Khan, T. A. Ponzio, G. Sanchez-Watts, B. G. Stanley, G. I. Hatton, and A. G. Watts Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine Neurons In Vivo and In Vitro: A Proposed Role during Glycemic Challenges J. Neurosci., July 4, 2007; 27(27): 7344 - 7360. [Abstract] [Full Text] [PDF]

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