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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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Reduction of hippocampal long-term potentiation but not long-term depression in neurabin KO mice.A, LTP is induced in hippocampal CA1 neurons with paring protocol in wild-type mice (n = 6). However, no LTP was induced in CA1 neurons in neurabin KO mice (n = 6). The insets show averages of six EPSCs at baseline response (pre, dark traces) and 30 min after (post, gray traces) LTP induction (arrow). The dashed line indicates the mean basal synaptic response. B, Statistical results showed significant loss of LTP in neurabin KO mice. C, LTD is induced in hippocampal CA1 neurons with paring protocol (−45 mV, 1 Hz, 300 pulses) in wild-type mice (n = 6). Similar LTD was observed in CA1 neurons in neurabin KO mice (n = 8). The insets show averages of six EPSCs at baseline response and 30 min after LTD induction (arrow). The dashed line indicates the mean basal synaptic response. D, Statistical results showed no significant difference (n.s.) in LTD between wild-type mice and neurabin KO mice. E, Post-tetanic potentiation is induced by stimulation of 100 Hz, 1s in wild-type mice (n = 9). F, Same stimulation protocol as E induced similar post-tetanic potentiation in neurabin KO mice (n = 12).
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pone-0001407-g002: Reduction of hippocampal long-term potentiation but not long-term depression in neurabin KO mice.A, LTP is induced in hippocampal CA1 neurons with paring protocol in wild-type mice (n = 6). However, no LTP was induced in CA1 neurons in neurabin KO mice (n = 6). The insets show averages of six EPSCs at baseline response (pre, dark traces) and 30 min after (post, gray traces) LTP induction (arrow). The dashed line indicates the mean basal synaptic response. B, Statistical results showed significant loss of LTP in neurabin KO mice. C, LTD is induced in hippocampal CA1 neurons with paring protocol (−45 mV, 1 Hz, 300 pulses) in wild-type mice (n = 6). Similar LTD was observed in CA1 neurons in neurabin KO mice (n = 8). The insets show averages of six EPSCs at baseline response and 30 min after LTD induction (arrow). The dashed line indicates the mean basal synaptic response. D, Statistical results showed no significant difference (n.s.) in LTD between wild-type mice and neurabin KO mice. E, Post-tetanic potentiation is induced by stimulation of 100 Hz, 1s in wild-type mice (n = 9). F, Same stimulation protocol as E induced similar post-tetanic potentiation in neurabin KO mice (n = 12).

Mentions: Hippocampal synaptic plasticity is known to be important for contextual fear memory [3], [29]. Therefore, we decided to study the role of neurabin in the synaptic plasticity, both LTP and LTD, in hippocampal CA1 pyramidal neurons. First, we investigated LTP in wild-type and neurabin KO mice. Evoked EPSCs were obtained by delivering focal electrical stimulation in striatum radium. LTP is reliably induced by the pairing protocol (see Methods) in the CA1 pyramidal neurons in wild-type mice (30 min after induction, 162.3±9.9 % of baseline response, n = 6; Fig. 2A and B). However, using the same protocol, a significantly smaller synaptic potentiation was induced in neurabin KO mice (107.6±9.4 % of baseline response, n = 6; Fig. 2A and B). To confirm the conclusion, we also studied spike-timing protocol-induced LTP (see Methods) in both groups. Similarly, there is a significant reduction of LTP in neurabin KO mice (96.6±1.4 % of baseline response, n = 6) compared to wild-type mice (135.9±10.5 % of baseline response, n = 5, P<0.01, unpaired t-test). Therefore, the deletion of neurabin abolished LTP in hippocampal CA1 pyramidal neurons.


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)

Reduction of hippocampal long-term potentiation but not long-term depression in neurabin KO mice.A, LTP is induced in hippocampal CA1 neurons with paring protocol in wild-type mice (n = 6). However, no LTP was induced in CA1 neurons in neurabin KO mice (n = 6). The insets show averages of six EPSCs at baseline response (pre, dark traces) and 30 min after (post, gray traces) LTP induction (arrow). The dashed line indicates the mean basal synaptic response. B, Statistical results showed significant loss of LTP in neurabin KO mice. C, LTD is induced in hippocampal CA1 neurons with paring protocol (−45 mV, 1 Hz, 300 pulses) in wild-type mice (n = 6). Similar LTD was observed in CA1 neurons in neurabin KO mice (n = 8). The insets show averages of six EPSCs at baseline response and 30 min after LTD induction (arrow). The dashed line indicates the mean basal synaptic response. D, Statistical results showed no significant difference (n.s.) in LTD between wild-type mice and neurabin KO mice. E, Post-tetanic potentiation is induced by stimulation of 100 Hz, 1s in wild-type mice (n = 9). F, Same stimulation protocol as E induced similar post-tetanic potentiation in neurabin KO mice (n = 12).
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Related In: Results  -  Collection

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

pone-0001407-g002: Reduction of hippocampal long-term potentiation but not long-term depression in neurabin KO mice.A, LTP is induced in hippocampal CA1 neurons with paring protocol in wild-type mice (n = 6). However, no LTP was induced in CA1 neurons in neurabin KO mice (n = 6). The insets show averages of six EPSCs at baseline response (pre, dark traces) and 30 min after (post, gray traces) LTP induction (arrow). The dashed line indicates the mean basal synaptic response. B, Statistical results showed significant loss of LTP in neurabin KO mice. C, LTD is induced in hippocampal CA1 neurons with paring protocol (−45 mV, 1 Hz, 300 pulses) in wild-type mice (n = 6). Similar LTD was observed in CA1 neurons in neurabin KO mice (n = 8). The insets show averages of six EPSCs at baseline response and 30 min after LTD induction (arrow). The dashed line indicates the mean basal synaptic response. D, Statistical results showed no significant difference (n.s.) in LTD between wild-type mice and neurabin KO mice. E, Post-tetanic potentiation is induced by stimulation of 100 Hz, 1s in wild-type mice (n = 9). F, Same stimulation protocol as E induced similar post-tetanic potentiation in neurabin KO mice (n = 12).
Mentions: Hippocampal synaptic plasticity is known to be important for contextual fear memory [3], [29]. Therefore, we decided to study the role of neurabin in the synaptic plasticity, both LTP and LTD, in hippocampal CA1 pyramidal neurons. First, we investigated LTP in wild-type and neurabin KO mice. Evoked EPSCs were obtained by delivering focal electrical stimulation in striatum radium. LTP is reliably induced by the pairing protocol (see Methods) in the CA1 pyramidal neurons in wild-type mice (30 min after induction, 162.3±9.9 % of baseline response, n = 6; Fig. 2A and B). However, using the same protocol, a significantly smaller synaptic potentiation was induced in neurabin KO mice (107.6±9.4 % of baseline response, n = 6; Fig. 2A and B). To confirm the conclusion, we also studied spike-timing protocol-induced LTP (see Methods) in both groups. Similarly, there is a significant reduction of LTP in neurabin KO mice (96.6±1.4 % of baseline response, n = 6) compared to wild-type mice (135.9±10.5 % of baseline response, n = 5, P<0.01, unpaired t-test). Therefore, the deletion of neurabin abolished LTP in hippocampal CA1 pyramidal neurons.

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