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Distance-dependent homeostatic synaptic scaling mediated by a-type potassium channels.

Ito HT, Schuman EM - Front Cell Neurosci (2009)

Bottom Line: Following A-type potassium channel inhibition for 12 h, recordings from CA1 somata revealed a significantly higher miniature excitatory postsynaptic current (mEPSC) frequency, whereas in dendritic recordings, there was no change in mEPSC frequency.Consistent with mEPSC recordings, we observed a significant increase in AMPA receptor density in stratum pyramidale but not stratum radiatum.Taken together, our results indicate that A-type potassium channels play an important role in controlling synaptic strength along the dendrites, which may help to maintain the computational capacity of the neuron.

View Article: PubMed Central - PubMed

Affiliation: Division of Biology, California Institute of Technology Pasadena, CA, USA.

ABSTRACT
Many lines of evidence suggest that the efficacy of synapses on CA1 pyramidal neuron dendrites increases as a function of distance from the cell body. The strength of an individual synapse is also dynamically modulated by activity-dependent synaptic plasticity, which raises the question as to how a neuron can reconcile individual synaptic changes with the maintenance of the proximal-to-distal gradient of synaptic strength along the dendrites. As the density of A-type potassium channels exhibits a similar gradient from proximal (low)-to-distal (high) dendrites, the A-current may play a role in coordinating local synaptic changes with the global synaptic strength gradient. Here we describe a form of homeostatic plasticity elicited by conventional activity blockade (with tetrodotoxin) coupled with a block of the A-type potassium channel. Following A-type potassium channel inhibition for 12 h, recordings from CA1 somata revealed a significantly higher miniature excitatory postsynaptic current (mEPSC) frequency, whereas in dendritic recordings, there was no change in mEPSC frequency. Consistent with mEPSC recordings, we observed a significant increase in AMPA receptor density in stratum pyramidale but not stratum radiatum. Based on these data, we propose that the differential distribution of A-type potassium channels along the apical dendrites may create a proximal-to-distal membrane potential gradient. This gradient may regulate AMPA receptor distribution along the same axis. Taken together, our results indicate that A-type potassium channels play an important role in controlling synaptic strength along the dendrites, which may help to maintain the computational capacity of the neuron.

No MeSH data available.


A chronically applied external electric field influences GluR1 distribution along the somatic-dendritic axis. (A) Resting membrane potentials measured from individual somata and dendrites of CA1 pyramidal neurons. The recording sites in dendrites were in the distal half of the stratum radiatum (approximately 300–350 μm away from soma). Data from individual experiments are represented by gray circles and black diamonds represent the mean. The application of 4AP (10 mM) abolished the voltage difference between soma and dendrites (n = 15 for each group) (*p < 0.05 in two-way ANOVA). (B) Scheme of apparatus used for the electric field-application to slices. The external electric field was applied to slices with a current source. The current amplitude was appropriately adjusted by monitoring the voltage difference between the two electrodes using a voltameter. The slices were treated with TTX (2 μM) + NBQX (20 μM) + APV (50 μM) to block neuronal activities. A chronic DC electric field (10 mV/mm) was applied to slices for 4 h. (C) The influence of the externally applied electric field on the GluR1 distribution. The relative somatic GluR1 signal intensity was significantly higher when the electric field was applied in a direction such that somatic side was negative relative to apical dendrites (n = 8 for each group) (*p < 0.05). (D) Slices were pretreated with a protein synthesis inhibitor, anisomycin (50 μM), beginning 30 min prior to the electric field-application. The external electric field was applied in the presence of TTX + NBQX + APV and anisomycin. Co-treatment with anisomycin abolished the GluR1 redistribution by the differentially applied chronic electric field (n = 7 for each group).
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Figure 8: A chronically applied external electric field influences GluR1 distribution along the somatic-dendritic axis. (A) Resting membrane potentials measured from individual somata and dendrites of CA1 pyramidal neurons. The recording sites in dendrites were in the distal half of the stratum radiatum (approximately 300–350 μm away from soma). Data from individual experiments are represented by gray circles and black diamonds represent the mean. The application of 4AP (10 mM) abolished the voltage difference between soma and dendrites (n = 15 for each group) (*p < 0.05 in two-way ANOVA). (B) Scheme of apparatus used for the electric field-application to slices. The external electric field was applied to slices with a current source. The current amplitude was appropriately adjusted by monitoring the voltage difference between the two electrodes using a voltameter. The slices were treated with TTX (2 μM) + NBQX (20 μM) + APV (50 μM) to block neuronal activities. A chronic DC electric field (10 mV/mm) was applied to slices for 4 h. (C) The influence of the externally applied electric field on the GluR1 distribution. The relative somatic GluR1 signal intensity was significantly higher when the electric field was applied in a direction such that somatic side was negative relative to apical dendrites (n = 8 for each group) (*p < 0.05). (D) Slices were pretreated with a protein synthesis inhibitor, anisomycin (50 μM), beginning 30 min prior to the electric field-application. The external electric field was applied in the presence of TTX + NBQX + APV and anisomycin. Co-treatment with anisomycin abolished the GluR1 redistribution by the differentially applied chronic electric field (n = 7 for each group).

Mentions: How do A-type potassium channels influence synaptic strength by an activity- or calcium-independent mechanism? Because A-type channels can be activated near the resting membrane potential of neurons (Hoffman et al., 1997), the distance-dependent distribution of A-type channels may differentially influence the resting membrane potential along the dendrites. To examine this idea, we directly measured the resting membrane potential either from the somata or dendrites of CA1 pyramidal neurons, using whole-cell recordings. In recordings conducted in control medium (ACSF + TTX), the resting membrane potential was significantly different between soma and dendrites (soma: −72.7 ± 0.44 mV, dendrites: −75.7 ± 0.65 mV; Figure 8A). However, when 4AP was applied to the slices, the observed difference in resting membrane potential was abolished (soma: −73.3 ± 0.62 mV, dendrites: −73.6 ± 0.55 mV; Figure 8A). Thus, A-type potassium channels appear to contribute to the voltage gradient along the dendrites, which may, in turn, modulate synaptic strength and GluR1 distribution.


Distance-dependent homeostatic synaptic scaling mediated by a-type potassium channels.

Ito HT, Schuman EM - Front Cell Neurosci (2009)

A chronically applied external electric field influences GluR1 distribution along the somatic-dendritic axis. (A) Resting membrane potentials measured from individual somata and dendrites of CA1 pyramidal neurons. The recording sites in dendrites were in the distal half of the stratum radiatum (approximately 300–350 μm away from soma). Data from individual experiments are represented by gray circles and black diamonds represent the mean. The application of 4AP (10 mM) abolished the voltage difference between soma and dendrites (n = 15 for each group) (*p < 0.05 in two-way ANOVA). (B) Scheme of apparatus used for the electric field-application to slices. The external electric field was applied to slices with a current source. The current amplitude was appropriately adjusted by monitoring the voltage difference between the two electrodes using a voltameter. The slices were treated with TTX (2 μM) + NBQX (20 μM) + APV (50 μM) to block neuronal activities. A chronic DC electric field (10 mV/mm) was applied to slices for 4 h. (C) The influence of the externally applied electric field on the GluR1 distribution. The relative somatic GluR1 signal intensity was significantly higher when the electric field was applied in a direction such that somatic side was negative relative to apical dendrites (n = 8 for each group) (*p < 0.05). (D) Slices were pretreated with a protein synthesis inhibitor, anisomycin (50 μM), beginning 30 min prior to the electric field-application. The external electric field was applied in the presence of TTX + NBQX + APV and anisomycin. Co-treatment with anisomycin abolished the GluR1 redistribution by the differentially applied chronic electric field (n = 7 for each group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 8: A chronically applied external electric field influences GluR1 distribution along the somatic-dendritic axis. (A) Resting membrane potentials measured from individual somata and dendrites of CA1 pyramidal neurons. The recording sites in dendrites were in the distal half of the stratum radiatum (approximately 300–350 μm away from soma). Data from individual experiments are represented by gray circles and black diamonds represent the mean. The application of 4AP (10 mM) abolished the voltage difference between soma and dendrites (n = 15 for each group) (*p < 0.05 in two-way ANOVA). (B) Scheme of apparatus used for the electric field-application to slices. The external electric field was applied to slices with a current source. The current amplitude was appropriately adjusted by monitoring the voltage difference between the two electrodes using a voltameter. The slices were treated with TTX (2 μM) + NBQX (20 μM) + APV (50 μM) to block neuronal activities. A chronic DC electric field (10 mV/mm) was applied to slices for 4 h. (C) The influence of the externally applied electric field on the GluR1 distribution. The relative somatic GluR1 signal intensity was significantly higher when the electric field was applied in a direction such that somatic side was negative relative to apical dendrites (n = 8 for each group) (*p < 0.05). (D) Slices were pretreated with a protein synthesis inhibitor, anisomycin (50 μM), beginning 30 min prior to the electric field-application. The external electric field was applied in the presence of TTX + NBQX + APV and anisomycin. Co-treatment with anisomycin abolished the GluR1 redistribution by the differentially applied chronic electric field (n = 7 for each group).
Mentions: How do A-type potassium channels influence synaptic strength by an activity- or calcium-independent mechanism? Because A-type channels can be activated near the resting membrane potential of neurons (Hoffman et al., 1997), the distance-dependent distribution of A-type channels may differentially influence the resting membrane potential along the dendrites. To examine this idea, we directly measured the resting membrane potential either from the somata or dendrites of CA1 pyramidal neurons, using whole-cell recordings. In recordings conducted in control medium (ACSF + TTX), the resting membrane potential was significantly different between soma and dendrites (soma: −72.7 ± 0.44 mV, dendrites: −75.7 ± 0.65 mV; Figure 8A). However, when 4AP was applied to the slices, the observed difference in resting membrane potential was abolished (soma: −73.3 ± 0.62 mV, dendrites: −73.6 ± 0.55 mV; Figure 8A). Thus, A-type potassium channels appear to contribute to the voltage gradient along the dendrites, which may, in turn, modulate synaptic strength and GluR1 distribution.

Bottom Line: Following A-type potassium channel inhibition for 12 h, recordings from CA1 somata revealed a significantly higher miniature excitatory postsynaptic current (mEPSC) frequency, whereas in dendritic recordings, there was no change in mEPSC frequency.Consistent with mEPSC recordings, we observed a significant increase in AMPA receptor density in stratum pyramidale but not stratum radiatum.Taken together, our results indicate that A-type potassium channels play an important role in controlling synaptic strength along the dendrites, which may help to maintain the computational capacity of the neuron.

View Article: PubMed Central - PubMed

Affiliation: Division of Biology, California Institute of Technology Pasadena, CA, USA.

ABSTRACT
Many lines of evidence suggest that the efficacy of synapses on CA1 pyramidal neuron dendrites increases as a function of distance from the cell body. The strength of an individual synapse is also dynamically modulated by activity-dependent synaptic plasticity, which raises the question as to how a neuron can reconcile individual synaptic changes with the maintenance of the proximal-to-distal gradient of synaptic strength along the dendrites. As the density of A-type potassium channels exhibits a similar gradient from proximal (low)-to-distal (high) dendrites, the A-current may play a role in coordinating local synaptic changes with the global synaptic strength gradient. Here we describe a form of homeostatic plasticity elicited by conventional activity blockade (with tetrodotoxin) coupled with a block of the A-type potassium channel. Following A-type potassium channel inhibition for 12 h, recordings from CA1 somata revealed a significantly higher miniature excitatory postsynaptic current (mEPSC) frequency, whereas in dendritic recordings, there was no change in mEPSC frequency. Consistent with mEPSC recordings, we observed a significant increase in AMPA receptor density in stratum pyramidale but not stratum radiatum. Based on these data, we propose that the differential distribution of A-type potassium channels along the apical dendrites may create a proximal-to-distal membrane potential gradient. This gradient may regulate AMPA receptor distribution along the same axis. Taken together, our results indicate that A-type potassium channels play an important role in controlling synaptic strength along the dendrites, which may help to maintain the computational capacity of the neuron.

No MeSH data available.