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, Herman H. Cheung, Elizabeth R. Gillard, Jennifer A. Palarca, Derek S. Welsbie, James W. Gurd, B. Glenn Stanley

Research output: Contribution to journalArticlepeer-review

Abstract

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 significandy suppressed feeding elicited by LHA NMDA injection (up to 69%) but only mildly suppressed deprivation feeding (24%), suggesting that PTKs maybe 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.

Original languageEnglish (US)
Pages (from-to)10603-10615
Number of pages13
JournalJournal of Neuroscience
Volume24
Issue number47
DOIs
StatePublished - Nov 24 2004
Externally publishedYes

Keywords

  • Eating
  • Feeding
  • Glutamate
  • Lateral hypothalamic area
  • NMDA
  • NR2A
  • NR2B
  • Pyk2
  • Signal transduction
  • Src
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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