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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.


Related in: MedlinePlus

The kinetics of the mEPSC waveform is not significantly different between TTX- and TTX + 4AP-treated slices. (A) The data in Figures 1A,B were reanalyzed using a different program for mEPSC detection (Mini Analysis, Synaptosoft), which is based on threshold-cutting for event amplitude and area, rather than template-matching as used in Figure 1 (Clampfit 9, Molecular Devices). The same pattern of results was obtained. (B) The averaged mEPSC waveforms detected by the Mini Analysis program were shown (top) (scale bar = 2 pA, 10 ms) (mEPSC waveforms were aligned at the 50% of rise time). The bottom figures show the mean rise (10–90% time point) and decay time (tau) of mEPSCs. No significant difference was observed in the kinetics of the mEPSC waveform between groups.
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Figure 3: The kinetics of the mEPSC waveform is not significantly different between TTX- and TTX + 4AP-treated slices. (A) The data in Figures 1A,B were reanalyzed using a different program for mEPSC detection (Mini Analysis, Synaptosoft), which is based on threshold-cutting for event amplitude and area, rather than template-matching as used in Figure 1 (Clampfit 9, Molecular Devices). The same pattern of results was obtained. (B) The averaged mEPSC waveforms detected by the Mini Analysis program were shown (top) (scale bar = 2 pA, 10 ms) (mEPSC waveforms were aligned at the 50% of rise time). The bottom figures show the mean rise (10–90% time point) and decay time (tau) of mEPSCs. No significant difference was observed in the kinetics of the mEPSC waveform between groups.

Mentions: Whole-cell voltage-clamp recordings from CA1 pyramidal neuron somata or dendrites were made (without visualization) with an Axopatch 200B (Axon Instruments). The internal solution of patch pipettes was as follows: for the miniature excitatory postsynaptic current (mEPSC) recordings (in mM) 115 cesium gluconate, 20 cesium chloride, 10 sodium phosphocreatine, 10 HEPES, 2 MgATP, 0.3 NaGTP (pH 7.3); for the measurement of the resting membrane potential (in mM) 115 potassium gluconate, 20 potassium chloride, 10 sodium phosphocreatine, 10 HEPES, 2 MgATP, 0.3 NaGTP (pH 7.3). After recovery from slicing or a pharmacological treatment, slices were transferred to a submerged recording chamber perfused with ACSF at 24.5–25.5°C or 32–34°C (for resting membrane potential recording). The mEPSC recordings were conducted in the presence of TTX (1 μM) and bicuculline (20 μM). Membrane voltage was clamped at −70 mV (without liquid junction potential correction). After recordings were stabilized, current traces were acquired for 3 min and all detected events were analyzed to calculate the mean amplitude and frequency of mEPSCs. The mEPSCs were detected using a template-matching algorithm from Clampfit 9 (Molecular Devices); the waveform template was made by averaging mEPSCs in untreated slices. In Figure 3, a different program for mEPSC detection (Mini Analysis, Synaptosoft) was used, which is based on threshold-cutting for event amplitude and area (threshold used for the analysis: amplitude > 5 pA, area > 10 fC). For the resting membrane potential measurement, potentials were corrected for liquid junction potentials, which were approximately −11 mV for TTX alone and −9 mV for TTX + 4AP (10 mM). Recordings were discarded when the series resistance was over 20 MΩ (50 MΩ in dendritic recordings) or either series or membrane resistance changed more than 20% during data acquisition. Data were collected by DigiData 1200 and pClamp 9 (Axon Instruments). All numerical values listed represent mean ± SEM, unless noted otherwise. The error bars in all figures represent SEM. A student's t-test was performed for all statistical analysis.


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

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

The kinetics of the mEPSC waveform is not significantly different between TTX- and TTX + 4AP-treated slices. (A) The data in Figures 1A,B were reanalyzed using a different program for mEPSC detection (Mini Analysis, Synaptosoft), which is based on threshold-cutting for event amplitude and area, rather than template-matching as used in Figure 1 (Clampfit 9, Molecular Devices). The same pattern of results was obtained. (B) The averaged mEPSC waveforms detected by the Mini Analysis program were shown (top) (scale bar = 2 pA, 10 ms) (mEPSC waveforms were aligned at the 50% of rise time). The bottom figures show the mean rise (10–90% time point) and decay time (tau) of mEPSCs. No significant difference was observed in the kinetics of the mEPSC waveform between groups.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2806179&req=5

Figure 3: The kinetics of the mEPSC waveform is not significantly different between TTX- and TTX + 4AP-treated slices. (A) The data in Figures 1A,B were reanalyzed using a different program for mEPSC detection (Mini Analysis, Synaptosoft), which is based on threshold-cutting for event amplitude and area, rather than template-matching as used in Figure 1 (Clampfit 9, Molecular Devices). The same pattern of results was obtained. (B) The averaged mEPSC waveforms detected by the Mini Analysis program were shown (top) (scale bar = 2 pA, 10 ms) (mEPSC waveforms were aligned at the 50% of rise time). The bottom figures show the mean rise (10–90% time point) and decay time (tau) of mEPSCs. No significant difference was observed in the kinetics of the mEPSC waveform between groups.
Mentions: Whole-cell voltage-clamp recordings from CA1 pyramidal neuron somata or dendrites were made (without visualization) with an Axopatch 200B (Axon Instruments). The internal solution of patch pipettes was as follows: for the miniature excitatory postsynaptic current (mEPSC) recordings (in mM) 115 cesium gluconate, 20 cesium chloride, 10 sodium phosphocreatine, 10 HEPES, 2 MgATP, 0.3 NaGTP (pH 7.3); for the measurement of the resting membrane potential (in mM) 115 potassium gluconate, 20 potassium chloride, 10 sodium phosphocreatine, 10 HEPES, 2 MgATP, 0.3 NaGTP (pH 7.3). After recovery from slicing or a pharmacological treatment, slices were transferred to a submerged recording chamber perfused with ACSF at 24.5–25.5°C or 32–34°C (for resting membrane potential recording). The mEPSC recordings were conducted in the presence of TTX (1 μM) and bicuculline (20 μM). Membrane voltage was clamped at −70 mV (without liquid junction potential correction). After recordings were stabilized, current traces were acquired for 3 min and all detected events were analyzed to calculate the mean amplitude and frequency of mEPSCs. The mEPSCs were detected using a template-matching algorithm from Clampfit 9 (Molecular Devices); the waveform template was made by averaging mEPSCs in untreated slices. In Figure 3, a different program for mEPSC detection (Mini Analysis, Synaptosoft) was used, which is based on threshold-cutting for event amplitude and area (threshold used for the analysis: amplitude > 5 pA, area > 10 fC). For the resting membrane potential measurement, potentials were corrected for liquid junction potentials, which were approximately −11 mV for TTX alone and −9 mV for TTX + 4AP (10 mM). Recordings were discarded when the series resistance was over 20 MΩ (50 MΩ in dendritic recordings) or either series or membrane resistance changed more than 20% during data acquisition. Data were collected by DigiData 1200 and pClamp 9 (Axon Instruments). All numerical values listed represent mean ± SEM, unless noted otherwise. The error bars in all figures represent SEM. A student's t-test was performed for all statistical analysis.

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.


Related in: MedlinePlus