The role of nitric oxide and somatic action potentials in a GluR1 independent LTP

Doctoral thesis English OPEN
Phillips, Keith Geoffrey
  • Subject: RC0321
    mesheuropmc: nervous system | musculoskeletal, neural, and ocular physiology

Studies in GluRl knockout mice have shown that neocortical LTP consist of both pre- and post-synaptic components that rely on nitric oxide and GluRl respectively (Hardingham and Fox, 2006). Given that GluRl knockout also show hippocampal LTP (Hoffmann et al., 2002) I hypothesised that the residual LTP might depend on nitric oxide. I have found that hippocampal LTP can be induced in GluRl knockout with purely orthodromic stimuli in mature mice (>8weeks) and that a theta-burst protocol was effective at inducing LTP while 100Hz stimulation was not. I found that only theta-burst stimulation produced reliable post-synaptic spikes, while 100Hz stimulation produced relatively few spikes. Inhibition of post-synaptic somatic spikes with local TTX application prevented LTP in the GluRl knockout mice. Theta-burst induced LTP in GluRl knockout was almost entirely nitric oxide dependent and involved both nitric oxide synthase 1 and nitric oxide synthase 3 isoforms. Finally, I also found that somatic spike production was also necessary for a nitric oxide dependent form of LTP in wild-type mice, which made up approximately 50% of the potentiation at 2 hours post-tetanus. I conclude that nitric oxide dependent LTP can be produced by physiologically relevant theta-burst stimuli because this protocol evokes reliable action potentials. Since this form of activity occurs during learning it could be relevant to memory formation in GluRl knockout and wild-type mice.
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