title: Evidence for TNFα action on excitatory and inhibitory neurotransmission in the central amygdala: a brain site influenced by stress.
abstract: Anxiety-like responses to stress are accompanied by elevation of brain cytokine-mRNAs. Because cytokines microinjected into central-amygdala (CeA) substitute for stress in a behavioral paradigm, the possibility was raised that cytokines increased by stress influence behavior by affecting CeA-neural activity. Previously, cytokines increased firing-rate of CeA-neurons comparable to that induced by corticotropin-releasing factor (CRF). In this investigation, tumor-necrosis-factor-α (TNFα) increased amplitude, but not frequency of mEPSCs from CeA-neurons. Additionally, TNFα decreased the threshold for triggering action potentials from CeA-neurons without altering membrane-properties during current-clamp recording. Glutamate-receptor-antagonist blockade of mEPSCs and the TNFα-induced reduction in firing threshold implicated glutamate in these changes. A phosphatidyl-inositol-3-kinase-antagonist prevented the TNFα-induced increased in amplitude of mEPSCs, documenting a TNFα intracellular influence. Additionally, TNFα increased frequency, but not amplitude of mIPSCs. CRF-receptor-antagonists were found to prevent the TNFα-induced increase in mIPSC-frequency, without altering the TNFα-induced amplitude increase in mEPSCs or the reduced threshold for action-potentials by TNFα. To clarify how TNFα was increasing CRF-release in the presence of tetrodotoxin, the possibility tested was whether preventing glial-activation would prevent this elevated mIPSC-frequency blocked by CRF-receptor antagonists. Minocycline, which blocks glial activation, prevented the TNFα-induced increase in mIPSC-frequency - a finding consistent with glia contributing to the CRF-involvement in this TNFα action. To fully understand the means by which a CRF1-receptor-antagonist and minocycline prevent TNFα from increasing mIPSC-frequency will require further clarification. Nonetheless, these data provide convincing evidence that release of TNFα by stress could alter neural activity of CeA-neurons by influencing GABA-and glutamate function.
authors.affiliation: Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ming
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Criswell
authors.forename: George R
authors.initials: GR
authors.lastname: Breese
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000276:immunology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009433:Neural Inhibition / Q000276:immunology*; D009474:Neurons / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000276:immunology*; D009435:Synaptic Transmission / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: CRF-receptor antagonists; Central amygdala; Glia; Minocycline; Neural function; PI-3-kinase-antagonist; mEPSCs; mIPSCs