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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

Impaired contextual but not auditory fear memory in neurabin KO mice.A, Contextual fear conditioning in neurabin KO mice (n = 6) is significantly reduced as compared with wild-type mice (n = 8) at 1 h and 1 and 3 d after training. B, Auditory fear conditioning in neurabin KO mice is similar to that in wild-type. C, There was no significant difference in response latencies between wild-type and neurabin KO mice in hotplate test. D, Spinal nociceptive tail-flick reflex between wild-type and neurabin KO mice is indistinguishable.
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pone-0001407-g001: Impaired contextual but not auditory fear memory in neurabin KO mice.A, Contextual fear conditioning in neurabin KO mice (n = 6) is significantly reduced as compared with wild-type mice (n = 8) at 1 h and 1 and 3 d after training. B, Auditory fear conditioning in neurabin KO mice is similar to that in wild-type. C, There was no significant difference in response latencies between wild-type and neurabin KO mice in hotplate test. D, Spinal nociceptive tail-flick reflex between wild-type and neurabin KO mice is indistinguishable.

Mentions: We assessed two forms of associative emotional memory in wild-type and neurabin KO mice: contextual and auditory fear conditioning. Contextual fear memory was first measured at 1 hour, 1 and 3 days after conditioning [28]. There was no significant difference in freezing responses immediately after training among wild-type mice (n = 8) and neurabin KO mice (n = 6), suggesting that the deletion of neurabin did not cause any developmental defect that would interfere with the shock-induced freezing response. However, neurabin KO mice showed a significant reduction in contextual fear memory one hour after conditioning (P<0.05, one-way ANOVA, Fig. 1A). The reduction in contextual fear memory lasted at one day (P<0.05) and three days (P<0.05) after conditioning (Fig. 1A). Unlike contextual fear memory, auditory fear memory was unaltered in neurabin KO mice (n = 6) compared with that of wild-type mice (n = 8; Fig. 1B).


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)

Impaired contextual but not auditory fear memory in neurabin KO mice.A, Contextual fear conditioning in neurabin KO mice (n = 6) is significantly reduced as compared with wild-type mice (n = 8) at 1 h and 1 and 3 d after training. B, Auditory fear conditioning in neurabin KO mice is similar to that in wild-type. C, There was no significant difference in response latencies between wild-type and neurabin KO mice in hotplate test. D, Spinal nociceptive tail-flick reflex between wild-type and neurabin KO mice is indistinguishable.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001407-g001: Impaired contextual but not auditory fear memory in neurabin KO mice.A, Contextual fear conditioning in neurabin KO mice (n = 6) is significantly reduced as compared with wild-type mice (n = 8) at 1 h and 1 and 3 d after training. B, Auditory fear conditioning in neurabin KO mice is similar to that in wild-type. C, There was no significant difference in response latencies between wild-type and neurabin KO mice in hotplate test. D, Spinal nociceptive tail-flick reflex between wild-type and neurabin KO mice is indistinguishable.
Mentions: We assessed two forms of associative emotional memory in wild-type and neurabin KO mice: contextual and auditory fear conditioning. Contextual fear memory was first measured at 1 hour, 1 and 3 days after conditioning [28]. There was no significant difference in freezing responses immediately after training among wild-type mice (n = 8) and neurabin KO mice (n = 6), suggesting that the deletion of neurabin did not cause any developmental defect that would interfere with the shock-induced freezing response. However, neurabin KO mice showed a significant reduction in contextual fear memory one hour after conditioning (P<0.05, one-way ANOVA, Fig. 1A). The reduction in contextual fear memory lasted at one day (P<0.05) and three days (P<0.05) after conditioning (Fig. 1A). Unlike contextual fear memory, auditory fear memory was unaltered in neurabin KO mice (n = 6) compared with that of wild-type mice (n = 8; Fig. 1B).

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