In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 24, No. 47 ( 2004-11-24), p. 10660-10669
Kurzfassung:
In neurons, neurogranin (Ng) binds calmodulin (CaM), and its binding affinity is reduced by increasing Ca 2+ , phosphorylation by PKC, or oxidation by oxidants. Ng concentration in the hippocampus of adult mice varied broadly (Ng +/+ , ∼160-370 and Ng +/- , ∼70-230 pmol/mg); the level in Ng +/+ mice is one of the highest among all neuronal CaM-binding proteins. Among Ng +/- mice, but less apparent in Ng +/+ , a significant relationship existed between their hippocampal levels of Ng and performances in the Morris water maze. Ng -/- mice performed poorly in this task; they also displayed deficits in high-frequency-induced long-term potentiation (LTP) in area CA1 of hippocampal slices, whereas low-frequency-induced long-term depression was enhanced. Thus, compared with Ng +/+ mice, the frequency-response curve of Ng -/- shifted to the right. Paired-pulse facilitation and synaptic fatigue during prolonged stimulation at 10 Hz (900 pulses) were unchanged in Ng -/- slices, indicating their normal presynaptic function. Measurements of Ca 2+ transients in CA1 pyramidal neurons after weak and strong tetanic stimulations (100 Hz, 400 and 1000 msec, respectively) revealed a significantly greater intracellular Ca 2+ ([Ca 2+ ] i ) response in Ng +/+ compared with Ng -/- mice, but the decay time constants did not differ. The diminished Ca 2+ dynamics in Ng -/- mice are a likely cause of their decreased propensity to undergo LTP. Thus, Ng may promote a high [Ca 2+ ] i by a “mass-action” mechanism; namely, the higher the Ng concentration, the more Ng-CaM complexes will be formed, which effectively raises [Ca 2+ ] i at any given Ca 2+ influx. This mechanism provides potent signal amplification in enhancing synaptic plasticity as well as learning and memory.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.2213-04.2004
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2004
ZDB Id:
1475274-8
SSG:
12
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