Evidence for the involvement of TNF and NF-kappa B in hippocampal synapticplasticity

The cytokine tumor necrosis factor-alpha (TNF), well-known for its roles in cellular responses to tissue injury, has recently been shown to be produce d in response to physiological activity in neuronal circuits. TNF stimulate s receptors in neurons linked to the activation of the transcription factor NF-kappa B, and recent findings suggest that this signaling pathway can mo dulate neuronal excitability and vulnerability of neurons to excitotoxicity . Because data indicate that TNF is produced, and NF-kappa B activated, und er conditions associated with learning and memory, we performed experiments in the hippocampal slice preparation aimed at elucidating roles for TNF an d NF-kappa B in modulating synaptic plasticity. Whereas stimulation of Scha ffer collateral axons at a frequency of 1 Hz induced long-term depression ( LTD) of synaptic transmission in region CA1 of wild-type mice, LTD did not occur in slices from TNF receptor knockout mice. Stimulation at 100 Hz indu ced long-term potentiation (LTP) in slices from both wild-type mice and mic e lacking TNF receptors. Basal transmission was unaltered in mice lacking T NF receptors. Pretreatment of slices from wild-type mice with kappa B decoy DNA prevented induction of LTD and significantly reduced the magnitude of LTP. Collectively, these data suggest important roles for TNF and signaling pathways that modulate NF-kappa B activity in regulation of hippocampal sy naptic plasticity. (C) 2000 Wiley-Liss, Inc.