Abstract
Inhibition of nerve growth and plasticity in the CNS is to a large part mediated by Nogo-like signaling, now encompassing a plethora of ligands, receptors, co-receptors and modulators. Here we describe the distribution and levels of mRNA encoding 11 key genes involved in Nogo-like signaling (Nogo-A, Oligodendrocyte-Myelin glycoprotein (OMgp), Nogo receptor 1 (NgR1), NgR2, NgR3, Lingo-1, TNF receptor orphan Y (Troy), Olfactomedin, Lateral olfactory tract usher substance (Lotus) and membrane-type matrix metalloproteinase-3 (MT3-MPP)), as well as BDNF and GAPDH. Expression was analyzed in nine different brain areas before, and at eight time points during the first 3 days after a strong neuroexcitatory stimulation, caused by one kainic acid injection. A temporo-spatial pattern of orderly transcriptional regulations emerges that strengthens the role of Nogo-signaling mechanisms for synaptic plasticity in synchrony with transcriptional increases of BDNF mRNA. For most Nogo-type signaling genes, the largest alterations of mRNA levels occur in the dentate gyrus, with marked alterations also in the CA1 region. Changes occurred somewhat later in several areas of the cerebral cortex. The detailed spatio-temporal pattern of mRNA presence and kainic acid-induced transcriptional response is gene-specific. We reveal that several different gene alterations combine to decrease (and later increase) Nogo-like signaling, as expected to allow structural plasticity responses. Other genes are altered in the opposite direction, suggesting that the system prepares in advance in order to rapidly restore balance. However, the fact that Lingo-1 shows a seemingly opposite, plasticity inhibiting response to kainic acid (strong increase of mRNA in the dentate gyrus), may instead suggest a plasticity-enhancing intracellular function of this presumed NgR1 co-receptor.
Highlights
The formation of lasting memories is the result of a large number of interacting mechanisms
We subsequently described how increased neuronal activity, as induced by kainic acid, upregulates the transcriptional activity of Nogo receptor 2 (NgR2), NgR3, and the Nogo receptor 1 (NgR1) antagonist Lotus immediately following a downregulation of NgR1
We find robust, gray matter-specific expression of NgR1mRNA in cerebral cortex, FIGURE 6 | Three day time course of alterations of NgR2 and NgR3 mRNA in response to kainic acid
Summary
The formation of lasting memories is the result of a large number of interacting mechanisms. In vivo imaging of newly formed postsynaptic sites in rodents suggests that individual synapses can exist for Stimulus-Regulation of Eleven Nogo-Signaling/Modulating Transcripts years, as required if the altered synaptic pattern is to carry lasting memories (Yang et al, 2009). Such alterations of synaptic patterns and the preservation of needed synapses are regulated by the concerted action of a large number of gene products.
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