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Biphasic somatic A-type K channel downregulation mediates intrinsic plasticity in hippocampal CA1 pyramidal neurons.

Jung SC, Hoffman DA - PLoS ONE (2009)

Bottom Line: Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+) channel inactivation along with a progressive, long-lasting decrease in peak A-current density.Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity.Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

View Article: PubMed Central - PubMed

Affiliation: Molecular Neurophysiology and Biophysics Unit, Laboratory of Cellular and Synaptic Neurophysiology, NICHD, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
Since its original description, the induction of synaptic long-term potentiation (LTP) has been known to be accompanied by a lasting increase in the intrinsic excitability (intrinsic plasticity) of hippocampal neurons. Recent evidence shows that dendritic excitability can be enhanced by an activity-dependent decrease in the activity of A-type K(+) channels. In the present manuscript, we examined the role of A-type K(+) channels in regulating intrinsic excitability of CA1 pyramidal neurons of the hippocampus after synapse-specific LTP induction. In electrophysiological recordings we found that LTP induced a potentiation of excitability which was accompanied by a two-phased change in A-type K(+) channel activity recorded in nucleated patches from organotypic slices of rat hippocampus. Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+) channel inactivation along with a progressive, long-lasting decrease in peak A-current density. Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity. These results suggest that two temporally distinct but overlapping mechanisms of A-channel downregulation together contribute to the plasticity of intrinsic excitability. Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

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Synaptic LTP decreases peak A-current density.A. Total A-current was acquired by subtracting the sustained current (obtained using a prepulse to inactivate IA as shown in the voltage protocol) from total current. Each trace is an average of three sweeps. In paired neurons showing potentiation of synaptic transmission, peak IA progressively decreased with time after LTP induction. Dashed line indicates control amplitude. Scale bars 500 pA, 100 ms. B. Summarized changes of peak amplitude of transient (left panel) and sustained (right panel) currents. Significant and progressive reduction of peak transient current was observed in paired neurons (red circles and bars) after conditioning stimulation without any changes of sustained currents. No change in peak A-current was observed in neurons not exhibiting a potentiation in synaptic strength (unpaired, green circles and bars). A significant increase in sustained current amplitude was observed in unpaired neurons 10 min after conditioning but this change was not lasting. Bars indicate the mean value of each group and semitransparent boxes represent SEM.
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pone-0006549-g004: Synaptic LTP decreases peak A-current density.A. Total A-current was acquired by subtracting the sustained current (obtained using a prepulse to inactivate IA as shown in the voltage protocol) from total current. Each trace is an average of three sweeps. In paired neurons showing potentiation of synaptic transmission, peak IA progressively decreased with time after LTP induction. Dashed line indicates control amplitude. Scale bars 500 pA, 100 ms. B. Summarized changes of peak amplitude of transient (left panel) and sustained (right panel) currents. Significant and progressive reduction of peak transient current was observed in paired neurons (red circles and bars) after conditioning stimulation without any changes of sustained currents. No change in peak A-current was observed in neurons not exhibiting a potentiation in synaptic strength (unpaired, green circles and bars). A significant increase in sustained current amplitude was observed in unpaired neurons 10 min after conditioning but this change was not lasting. Bars indicate the mean value of each group and semitransparent boxes represent SEM.

Mentions: Our previous report demonstrating the activity-dependent downregulation of IA in cultured neurons suggested another possible mechanism by which IA could contribute to intrinsic plasticity[12]. Here, we measured peak IA in nucleated patches for voltage steps from −120 mV to +60 mV (Figure 4A). Peak IA before conditioning stimulation averaged 1.5 nA (Figure 4A and B, control = 1.52±0.11 nA). In neurons receiving unpaired stimulation, which did not show synaptic potentiation, no reduction of peak IA was observed (Figure 4A and B; “Unpaired”, 30 min = 1.37±0.12 nA, p = 0.441, compared with “control”). However, a significant and time-dependent decrement of IA peak was observed in neurons exhibiting synaptic potentiation after paired stimulation (Figure 4A and B). Peak IA decreased by about 30%, 10 min after LTP induction (“Paired”, 10 min = 1.10±0.06 nA, p = 0.009) and by 30 min, less than half the “control” level of IA remained (“Paired”, 30 min = 0.69±0.05 nA, p<0.001). No change, at any time point was observed after LTP induction for the sustained, non-inactivating component of the total outward current (Figure 4). However, a small but significant increase of sustained current was observed in unpaired neurons 10 min after conditioning stimulation, compared with “control” (control = 0.23±0.01; “Unpaired”, 10 min = 0.32±0.03 nA, p = 0.016). This increase did not persist beyond the initial 10 min time point (30 min, paired = 0.27±0.02, unpaired = 0.26±0.02 nA).


Biphasic somatic A-type K channel downregulation mediates intrinsic plasticity in hippocampal CA1 pyramidal neurons.

Jung SC, Hoffman DA - PLoS ONE (2009)

Synaptic LTP decreases peak A-current density.A. Total A-current was acquired by subtracting the sustained current (obtained using a prepulse to inactivate IA as shown in the voltage protocol) from total current. Each trace is an average of three sweeps. In paired neurons showing potentiation of synaptic transmission, peak IA progressively decreased with time after LTP induction. Dashed line indicates control amplitude. Scale bars 500 pA, 100 ms. B. Summarized changes of peak amplitude of transient (left panel) and sustained (right panel) currents. Significant and progressive reduction of peak transient current was observed in paired neurons (red circles and bars) after conditioning stimulation without any changes of sustained currents. No change in peak A-current was observed in neurons not exhibiting a potentiation in synaptic strength (unpaired, green circles and bars). A significant increase in sustained current amplitude was observed in unpaired neurons 10 min after conditioning but this change was not lasting. Bars indicate the mean value of each group and semitransparent boxes represent SEM.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2717216&req=5

pone-0006549-g004: Synaptic LTP decreases peak A-current density.A. Total A-current was acquired by subtracting the sustained current (obtained using a prepulse to inactivate IA as shown in the voltage protocol) from total current. Each trace is an average of three sweeps. In paired neurons showing potentiation of synaptic transmission, peak IA progressively decreased with time after LTP induction. Dashed line indicates control amplitude. Scale bars 500 pA, 100 ms. B. Summarized changes of peak amplitude of transient (left panel) and sustained (right panel) currents. Significant and progressive reduction of peak transient current was observed in paired neurons (red circles and bars) after conditioning stimulation without any changes of sustained currents. No change in peak A-current was observed in neurons not exhibiting a potentiation in synaptic strength (unpaired, green circles and bars). A significant increase in sustained current amplitude was observed in unpaired neurons 10 min after conditioning but this change was not lasting. Bars indicate the mean value of each group and semitransparent boxes represent SEM.
Mentions: Our previous report demonstrating the activity-dependent downregulation of IA in cultured neurons suggested another possible mechanism by which IA could contribute to intrinsic plasticity[12]. Here, we measured peak IA in nucleated patches for voltage steps from −120 mV to +60 mV (Figure 4A). Peak IA before conditioning stimulation averaged 1.5 nA (Figure 4A and B, control = 1.52±0.11 nA). In neurons receiving unpaired stimulation, which did not show synaptic potentiation, no reduction of peak IA was observed (Figure 4A and B; “Unpaired”, 30 min = 1.37±0.12 nA, p = 0.441, compared with “control”). However, a significant and time-dependent decrement of IA peak was observed in neurons exhibiting synaptic potentiation after paired stimulation (Figure 4A and B). Peak IA decreased by about 30%, 10 min after LTP induction (“Paired”, 10 min = 1.10±0.06 nA, p = 0.009) and by 30 min, less than half the “control” level of IA remained (“Paired”, 30 min = 0.69±0.05 nA, p<0.001). No change, at any time point was observed after LTP induction for the sustained, non-inactivating component of the total outward current (Figure 4). However, a small but significant increase of sustained current was observed in unpaired neurons 10 min after conditioning stimulation, compared with “control” (control = 0.23±0.01; “Unpaired”, 10 min = 0.32±0.03 nA, p = 0.016). This increase did not persist beyond the initial 10 min time point (30 min, paired = 0.27±0.02, unpaired = 0.26±0.02 nA).

Bottom Line: Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+) channel inactivation along with a progressive, long-lasting decrease in peak A-current density.Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity.Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

View Article: PubMed Central - PubMed

Affiliation: Molecular Neurophysiology and Biophysics Unit, Laboratory of Cellular and Synaptic Neurophysiology, NICHD, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
Since its original description, the induction of synaptic long-term potentiation (LTP) has been known to be accompanied by a lasting increase in the intrinsic excitability (intrinsic plasticity) of hippocampal neurons. Recent evidence shows that dendritic excitability can be enhanced by an activity-dependent decrease in the activity of A-type K(+) channels. In the present manuscript, we examined the role of A-type K(+) channels in regulating intrinsic excitability of CA1 pyramidal neurons of the hippocampus after synapse-specific LTP induction. In electrophysiological recordings we found that LTP induced a potentiation of excitability which was accompanied by a two-phased change in A-type K(+) channel activity recorded in nucleated patches from organotypic slices of rat hippocampus. Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+) channel inactivation along with a progressive, long-lasting decrease in peak A-current density. Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity. These results suggest that two temporally distinct but overlapping mechanisms of A-channel downregulation together contribute to the plasticity of intrinsic excitability. Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

Show MeSH
Related in: MedlinePlus