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Neurabin contributes to hippocampal long-term potentiation and contextual fear memory.

Wu LJ, Ren M, Wang H, Kim SS, Cao X, Zhuo M - PLoS ONE (2008)

Bottom Line: Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation.However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions.Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Toronto, Toronto, Onatrio, Canada.

ABSTRACT
Neurabin is a scaffolding protein that interacts with actin and protein phosphatase-1. Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation. However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions. Using neurabin knockout (KO) mice, here we studied the function of neurabin in hippocampal synaptic transmission, plasticity and behavioral memory. We demonstrated that neurabin KO mice showed a deficit in contextual fear memory but not auditory fear memory. Whole-cell patch clamp recordings in the hippocampal CA1 neurons showed that long-term potentiation (LTP) was significantly reduced, whereas long-term depression (LTD) was unaltered in neurabin KO mice. Moreover, increased AMPA receptor but not NMDA receptor-mediated synaptic transmission was found in neurabin KO mice, and is accompanied by decreased phosphorylation of GluR1 at the PKA site (Ser845) but no change at the CaMKII/PKC site (Ser831). Pre-conditioning with LTD induction rescued the following LTP in neurabin KO mice, suggesting the loss of LTP may be due to the saturated synaptic transmission. Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.

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Related in: MedlinePlus

Increased hippocampal AMPA receptor-mediated EPSCs and altered GluR1 phosphorylation in neurabin KO mice.A, Representative traces of AMPA receptor-mediated EPSCs evoked by series of stimulations in wild-type and neurabin KO mice B, Input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO (n = 6) and wild-type (n = 6) mice. There is a significant increase of input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO mice. C and D, Current-voltage plots for AMPA receptor-mediated EPSCs in neurabin KO (n = 7) and wild-type mice (n = 7). There were no significant difference between neurabin KO mice and wild-type mice. E, Western blot showing total expression of GluR1 and GluR2&3 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). F, Western blot showing phosphorylation of GluR1 at sites of Ser845 and Ser831 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). G, Summarized results showing the relative expression of GluR1, GluR2&3, and p-Ser845 and p-Ser831 on GluR1, in neurabin KO mice (n =  4 mice) compared with those in wild-type mice (n = 4 mice). Only p-Ser845 is significantly reduced in the KO mice.
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pone-0001407-g004: Increased hippocampal AMPA receptor-mediated EPSCs and altered GluR1 phosphorylation in neurabin KO mice.A, Representative traces of AMPA receptor-mediated EPSCs evoked by series of stimulations in wild-type and neurabin KO mice B, Input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO (n = 6) and wild-type (n = 6) mice. There is a significant increase of input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO mice. C and D, Current-voltage plots for AMPA receptor-mediated EPSCs in neurabin KO (n = 7) and wild-type mice (n = 7). There were no significant difference between neurabin KO mice and wild-type mice. E, Western blot showing total expression of GluR1 and GluR2&3 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). F, Western blot showing phosphorylation of GluR1 at sites of Ser845 and Ser831 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). G, Summarized results showing the relative expression of GluR1, GluR2&3, and p-Ser845 and p-Ser831 on GluR1, in neurabin KO mice (n =  4 mice) compared with those in wild-type mice (n = 4 mice). Only p-Ser845 is significantly reduced in the KO mice.

Mentions: Because the neurabin-binding protein, PP1, is well known to regulate AMPA receptor activity [32], we wanted to know whether the basal synaptic transmission was altered in neurabin KO mice. To address this question, we analyzed the input-output relationship of AMPA receptor-mediated EPSCs in wild-type and neurabin KO mice. We found that AMPA receptor-mediated EPSCs in neurabin KO mice (n = 6) were significantly increased compared to those in wild-type mice (n = 6, P<0.05, two-way ANOVA; Fig. 4A and B). The enhanced EPSCs are not due to the possible change in the voltage dependence of AMPA receptor-mediated currents, since the I-V relationship of AMPA receptor-mediated EPSCs between neurabin KO mice (n = 7) and wild-type mice (n = 7; P>0.05, two-way ANOVA) is similar (Fig. 4C and D). Therefore, these results indicate that while electrophysiological properties of AMPA receptors remain unchanged, the AMPA receptor mediated responses are enhanced in neurabin KO mice.


Neurabin contributes to hippocampal long-term potentiation and contextual fear memory.

Wu LJ, Ren M, Wang H, Kim SS, Cao X, Zhuo M - PLoS ONE (2008)

Increased hippocampal AMPA receptor-mediated EPSCs and altered GluR1 phosphorylation in neurabin KO mice.A, Representative traces of AMPA receptor-mediated EPSCs evoked by series of stimulations in wild-type and neurabin KO mice B, Input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO (n = 6) and wild-type (n = 6) mice. There is a significant increase of input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO mice. C and D, Current-voltage plots for AMPA receptor-mediated EPSCs in neurabin KO (n = 7) and wild-type mice (n = 7). There were no significant difference between neurabin KO mice and wild-type mice. E, Western blot showing total expression of GluR1 and GluR2&3 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). F, Western blot showing phosphorylation of GluR1 at sites of Ser845 and Ser831 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). G, Summarized results showing the relative expression of GluR1, GluR2&3, and p-Ser845 and p-Ser831 on GluR1, in neurabin KO mice (n =  4 mice) compared with those in wild-type mice (n = 4 mice). Only p-Ser845 is significantly reduced in the KO mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169299&req=5

pone-0001407-g004: Increased hippocampal AMPA receptor-mediated EPSCs and altered GluR1 phosphorylation in neurabin KO mice.A, Representative traces of AMPA receptor-mediated EPSCs evoked by series of stimulations in wild-type and neurabin KO mice B, Input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO (n = 6) and wild-type (n = 6) mice. There is a significant increase of input-output relationship for AMPA receptor-mediated EPSCs in neurabin KO mice. C and D, Current-voltage plots for AMPA receptor-mediated EPSCs in neurabin KO (n = 7) and wild-type mice (n = 7). There were no significant difference between neurabin KO mice and wild-type mice. E, Western blot showing total expression of GluR1 and GluR2&3 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). F, Western blot showing phosphorylation of GluR1 at sites of Ser845 and Ser831 in neurabin KO mice (n = 4 mice) and wild-type mice (n = 4 mice). G, Summarized results showing the relative expression of GluR1, GluR2&3, and p-Ser845 and p-Ser831 on GluR1, in neurabin KO mice (n =  4 mice) compared with those in wild-type mice (n = 4 mice). Only p-Ser845 is significantly reduced in the KO mice.
Mentions: Because the neurabin-binding protein, PP1, is well known to regulate AMPA receptor activity [32], we wanted to know whether the basal synaptic transmission was altered in neurabin KO mice. To address this question, we analyzed the input-output relationship of AMPA receptor-mediated EPSCs in wild-type and neurabin KO mice. We found that AMPA receptor-mediated EPSCs in neurabin KO mice (n = 6) were significantly increased compared to those in wild-type mice (n = 6, P<0.05, two-way ANOVA; Fig. 4A and B). The enhanced EPSCs are not due to the possible change in the voltage dependence of AMPA receptor-mediated currents, since the I-V relationship of AMPA receptor-mediated EPSCs between neurabin KO mice (n = 7) and wild-type mice (n = 7; P>0.05, two-way ANOVA) is similar (Fig. 4C and D). Therefore, these results indicate that while electrophysiological properties of AMPA receptors remain unchanged, the AMPA receptor mediated responses are enhanced in neurabin KO mice.

Bottom Line: Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation.However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions.Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Toronto, Toronto, Onatrio, Canada.

ABSTRACT
Neurabin is a scaffolding protein that interacts with actin and protein phosphatase-1. Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation. However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions. Using neurabin knockout (KO) mice, here we studied the function of neurabin in hippocampal synaptic transmission, plasticity and behavioral memory. We demonstrated that neurabin KO mice showed a deficit in contextual fear memory but not auditory fear memory. Whole-cell patch clamp recordings in the hippocampal CA1 neurons showed that long-term potentiation (LTP) was significantly reduced, whereas long-term depression (LTD) was unaltered in neurabin KO mice. Moreover, increased AMPA receptor but not NMDA receptor-mediated synaptic transmission was found in neurabin KO mice, and is accompanied by decreased phosphorylation of GluR1 at the PKA site (Ser845) but no change at the CaMKII/PKC site (Ser831). Pre-conditioning with LTD induction rescued the following LTP in neurabin KO mice, suggesting the loss of LTP may be due to the saturated synaptic transmission. Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.

Show MeSH
Related in: MedlinePlus