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Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation.

Bencsik N, Szíber Z, Liliom H, Tárnok K, Borbély S, Gulyás M, Rátkai A, Szűcs A, Hazai-Novák D, Ellwanger K, Rácz B, Pfizenmaier K, Hausser A, Schlett K - J. Cell Biol. (2015)

Bottom Line: In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways.Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation.We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

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Affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.

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Inhibition of endogenous PKD activity in hippocampal pyramidal neurons selectively impairs spatial memory formation and reduces LTP in CA1 hippocampal neurons. Control (n = 16) and kdPKD-EGFP–expressing (n = 16) data are displayed by open and closed symbols and columns, respectively (B, C, and E–L). (A and B) Duration of time spent (A) and total running distance (B) within the open field. (C) Animals performed novel object recognition tests similarly before and during 12 wk of DOX. (D) Representative trajectories from control and kdPKD-EGFP–expressing mice during the second probe trial of the Morris water maze. Black triangles indicate start positions; the inner circles represent the target area over the original platform. (E) Distance swam within the target area during the first (day 5) and second (day 10) probe trials. (F) Mean distance needed to find all baits in the radial maze during the teaching process. (G) Mean POPS amplitudes evoked by single stimuli via SCs (SC stim) or MFs (MF stim). (H) Stimulation paradigm during LTP induction. (I and J) Relative POPS amplitudes after a 100-Hz HFS of the SCs (SC stim; I) or MFs (MF stim; J). (K and L) E/S curves describing POPS amplitudes in relation to the slope of the extracellular postsynaptic excitatory responses (dEPSP) determined in CA1 neurons before (K) or after (L) tetanization of the SCs. All data are shown as mean ± SEM. *, P < 0.05; **, P < 0.01.
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fig5: Inhibition of endogenous PKD activity in hippocampal pyramidal neurons selectively impairs spatial memory formation and reduces LTP in CA1 hippocampal neurons. Control (n = 16) and kdPKD-EGFP–expressing (n = 16) data are displayed by open and closed symbols and columns, respectively (B, C, and E–L). (A and B) Duration of time spent (A) and total running distance (B) within the open field. (C) Animals performed novel object recognition tests similarly before and during 12 wk of DOX. (D) Representative trajectories from control and kdPKD-EGFP–expressing mice during the second probe trial of the Morris water maze. Black triangles indicate start positions; the inner circles represent the target area over the original platform. (E) Distance swam within the target area during the first (day 5) and second (day 10) probe trials. (F) Mean distance needed to find all baits in the radial maze during the teaching process. (G) Mean POPS amplitudes evoked by single stimuli via SCs (SC stim) or MFs (MF stim). (H) Stimulation paradigm during LTP induction. (I and J) Relative POPS amplitudes after a 100-Hz HFS of the SCs (SC stim; I) or MFs (MF stim; J). (K and L) E/S curves describing POPS amplitudes in relation to the slope of the extracellular postsynaptic excitatory responses (dEPSP) determined in CA1 neurons before (K) or after (L) tetanization of the SCs. All data are shown as mean ± SEM. *, P < 0.05; **, P < 0.01.

Mentions: To assess neuron-specific functions of PKD in vivo, we used a transgenic TetOn mouse line, allowing inducible expression of the dominant-negative kdPKD-EGFP protein (Czöndör et al., 2009). For better readability, doxycycline (DOX)-treated CaMKIIα-rtTA2 × kdPKD-EGFP double transgenic mice are named kdPKD-EGFP–expressing mice, whereas single transgenic littermates treated with DOX are referred to as the control group (Fig. 4, and Fig. 5, and Fig. S3).


Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation.

Bencsik N, Szíber Z, Liliom H, Tárnok K, Borbély S, Gulyás M, Rátkai A, Szűcs A, Hazai-Novák D, Ellwanger K, Rácz B, Pfizenmaier K, Hausser A, Schlett K - J. Cell Biol. (2015)

Inhibition of endogenous PKD activity in hippocampal pyramidal neurons selectively impairs spatial memory formation and reduces LTP in CA1 hippocampal neurons. Control (n = 16) and kdPKD-EGFP–expressing (n = 16) data are displayed by open and closed symbols and columns, respectively (B, C, and E–L). (A and B) Duration of time spent (A) and total running distance (B) within the open field. (C) Animals performed novel object recognition tests similarly before and during 12 wk of DOX. (D) Representative trajectories from control and kdPKD-EGFP–expressing mice during the second probe trial of the Morris water maze. Black triangles indicate start positions; the inner circles represent the target area over the original platform. (E) Distance swam within the target area during the first (day 5) and second (day 10) probe trials. (F) Mean distance needed to find all baits in the radial maze during the teaching process. (G) Mean POPS amplitudes evoked by single stimuli via SCs (SC stim) or MFs (MF stim). (H) Stimulation paradigm during LTP induction. (I and J) Relative POPS amplitudes after a 100-Hz HFS of the SCs (SC stim; I) or MFs (MF stim; J). (K and L) E/S curves describing POPS amplitudes in relation to the slope of the extracellular postsynaptic excitatory responses (dEPSP) determined in CA1 neurons before (K) or after (L) tetanization of the SCs. All data are shown as mean ± SEM. *, P < 0.05; **, P < 0.01.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4555815&req=5

fig5: Inhibition of endogenous PKD activity in hippocampal pyramidal neurons selectively impairs spatial memory formation and reduces LTP in CA1 hippocampal neurons. Control (n = 16) and kdPKD-EGFP–expressing (n = 16) data are displayed by open and closed symbols and columns, respectively (B, C, and E–L). (A and B) Duration of time spent (A) and total running distance (B) within the open field. (C) Animals performed novel object recognition tests similarly before and during 12 wk of DOX. (D) Representative trajectories from control and kdPKD-EGFP–expressing mice during the second probe trial of the Morris water maze. Black triangles indicate start positions; the inner circles represent the target area over the original platform. (E) Distance swam within the target area during the first (day 5) and second (day 10) probe trials. (F) Mean distance needed to find all baits in the radial maze during the teaching process. (G) Mean POPS amplitudes evoked by single stimuli via SCs (SC stim) or MFs (MF stim). (H) Stimulation paradigm during LTP induction. (I and J) Relative POPS amplitudes after a 100-Hz HFS of the SCs (SC stim; I) or MFs (MF stim; J). (K and L) E/S curves describing POPS amplitudes in relation to the slope of the extracellular postsynaptic excitatory responses (dEPSP) determined in CA1 neurons before (K) or after (L) tetanization of the SCs. All data are shown as mean ± SEM. *, P < 0.05; **, P < 0.01.
Mentions: To assess neuron-specific functions of PKD in vivo, we used a transgenic TetOn mouse line, allowing inducible expression of the dominant-negative kdPKD-EGFP protein (Czöndör et al., 2009). For better readability, doxycycline (DOX)-treated CaMKIIα-rtTA2 × kdPKD-EGFP double transgenic mice are named kdPKD-EGFP–expressing mice, whereas single transgenic littermates treated with DOX are referred to as the control group (Fig. 4, and Fig. 5, and Fig. S3).

Bottom Line: In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways.Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation.We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.

Show MeSH
Related in: MedlinePlus