Neurogranin/RC3 Enhances Long-Term Potentiation and Learning by Promoting Calcium-Mediated Signaling

Abstract

] i by a "mass-action" mechanism; namely, the higher the Ng concentration, the more Ng-CaM complexes will be formed, which effectively raises [Ca 2ϩ ] i at any given Ca 2ϩ influx. This mechanism provides potent signal amplification in enhancing synaptic plasticity as well as learning and memory.

Role of the Neurogranin Concentrated in Spines in the Induction of Long-Term Potentiation

“…Injection of antibodies to Ng into hippocampal CA1 pyramidal cells prevented induction of LTP in these neurons (Fedorov et al, 1995). In agreement with this finding, knockout of Ng resulted in a large decrease in the LTP induced by a single 100 Hz, 1 s tetanus, whereas LTD was slightly enhanced (Huang et al, 2004). Quite different effects were reported by Krucker et al (2002), probably because in the latter case, the Ng gene was replaced with a construct that retained an N-terminal peptide of Ng.…”

“…At low [Ca 2ϩ ], most of the CaM is bound to Ng and GAP-43. According to Huang et al (2004) the concentration of Ng in the hippocampus is 1.9 g/mg protein. Taking brain protein content as 8% yields an average concentration of Ng in neurons of ϳ20 M. Punctate staining of Ng is indicative of a much higher than average concentration in dendritic spines (Watson et al, 1992;NeunerJehle et al, 1996).…”

Investigations of transcript expression in fathead minnow (Pimephales promelas) brain tissue reveal toxicological impacts of RDX exposure

“…In conjunction with the observed impacts on calmodulin expression, RDX also impaired transcript expression of calcineurin B, the regulatory subunit of calciuneurin Ca2+ binding site which is also involved in calmodulin and Ca2+ dependent signal transduction pathways (Rusnak and Mertz, 2000). Neurogranin, expressed solely in brain tissue with the highest expression in dendritic spines, binds to calmodulin when Ca2+ levels are low or absent and therefore affects Ca2+ and Ca-calmodulin signaling pathways by serving as a Ca2+ capacitor (Gerendasy and Sutcliffe, 1997;Huang et al, 2004;Chakravarthy et al, 1999). By acting as a capacitor, neurogranin not only plays a role in signaling but learning, memory, and neural plasticity as well (Pak et al, 2000;Gerendasy and Sutcliffe, 1997;Huang et al, 2004).…”

“…Neurogranin, expressed solely in brain tissue with the highest expression in dendritic spines, binds to calmodulin when Ca2+ levels are low or absent and therefore affects Ca2+ and Ca-calmodulin signaling pathways by serving as a Ca2+ capacitor (Gerendasy and Sutcliffe, 1997;Huang et al, 2004;Chakravarthy et al, 1999). By acting as a capacitor, neurogranin not only plays a role in signaling but learning, memory, and neural plasticity as well (Pak et al, 2000;Gerendasy and Sutcliffe, 1997;Huang et al, 2004). In an event of neuronal over-excitation of glutamate receptors, as discussed above, reduced neurogranin transcription may be the result of excess production of NO by nNOS (Gui et al, 2007;Wu et al, 2003).…”

“…In an event of neuronal over-excitation of glutamate receptors, as discussed above, reduced neurogranin transcription may be the result of excess production of NO by nNOS (Gui et al, 2007;Wu et al, 2003). Oxidants produced due to oxidative stress, can decrease the binding affinity between neurogranin and calmodulin (Huang et al, 2004) impacting signal transduction. The RDX-related impacts on calcium binding and signaling indicate the potential for impacts on neurophysiology and signal transduction in fathead minnow brain tissue.…”