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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

An externally applied electric field does not influence the movement of GluR1-GFP. (A) GluR1-GFP was expressed in hippocampal dissociated culture neurons by a Sindbis virus expression system. The images were taken every 10 s. After taking 10 baseline images, a region that included the soma and the distal dendrites (green boxes) was photobleached, leaving a 25 μm length segment in proximal dendrite. Then, the photobleaching was repeated after every 5 images acquired. For the experiments with the electric-field application, a 10 mV/mm of external electric field was continuously applied along the primary dendrites once the photobleaching started (scale bar = 12.5 μm). (B) Analysis of fluorescence decay in the 25 μm segment in proximal dendrite. No significant difference was observed in fluorescence decay under the external electric-field application, suggesting that the electric field does not influence GluR1-GFP movement, directly (n = 5).
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Figure 10: An externally applied electric field does not influence the movement of GluR1-GFP. (A) GluR1-GFP was expressed in hippocampal dissociated culture neurons by a Sindbis virus expression system. The images were taken every 10 s. After taking 10 baseline images, a region that included the soma and the distal dendrites (green boxes) was photobleached, leaving a 25 μm length segment in proximal dendrite. Then, the photobleaching was repeated after every 5 images acquired. For the experiments with the electric-field application, a 10 mV/mm of external electric field was continuously applied along the primary dendrites once the photobleaching started (scale bar = 12.5 μm). (B) Analysis of fluorescence decay in the 25 μm segment in proximal dendrite. No significant difference was observed in fluorescence decay under the external electric-field application, suggesting that the electric field does not influence GluR1-GFP movement, directly (n = 5).

Mentions: If a dendritic electric field generated by a voltage gradient along the dendritic axis regulates GluR1 distribution, then an externally applied electric field might be able to similarly alter GluR1 distribution. We tested this hypothesis by applying a chronic electric field, parallel to the main apical dendritic axis, to hippocampal slices (Figure 8B; see Materials and Methods for detail) and then measuring GluR1 distribution using immunohistochemical techniques. The field was applied for 4 h, with the somatic region representing either the positive or negative pole. Following chronic field stimulation, we found that GluR1 distribution was significantly influenced in a direction-sensitive manner (signal ratio of s. pyramidale to s. radiatum: soma positive 0.76 ± 0.06, soma negative 1.05 ± 0.08; Figure 8C). Corresponding to the GluR1 distribution, we found that mEPSC frequency was also significantly influenced by an external electric field-application in a direction-sensitive manner (mEPSC amplitude: soma positive 12.01 ± 0.40 pA, soma negative 12.52 ± 0.29 pA; mEPSC frequency: soma positive 0.83 ± 0.09 Hz, soma positive 1.15 ± 0.07 Hz; Figure 9). Furthermore, this differential electric-field induced change in GluR1 distribution was completely abolished by the addition of a protein-synthesis inhibitor, anisomycin (soma positive: 0.82 ± 0.07, soma negative: 0.78 ± 0.06; Figure 8D). Fluorescence-loss-in-photobleaching experiments in neurons expressing a GluR1-GFP fusion protein argue against a direct effect of electric field on GluR1 movement (Figure 10). These results show that a modest change in the electric field along the dendritic axis is sufficient to elicit a protein-synthesis dependent change in the distribution of GluR1.


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

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

An externally applied electric field does not influence the movement of GluR1-GFP. (A) GluR1-GFP was expressed in hippocampal dissociated culture neurons by a Sindbis virus expression system. The images were taken every 10 s. After taking 10 baseline images, a region that included the soma and the distal dendrites (green boxes) was photobleached, leaving a 25 μm length segment in proximal dendrite. Then, the photobleaching was repeated after every 5 images acquired. For the experiments with the electric-field application, a 10 mV/mm of external electric field was continuously applied along the primary dendrites once the photobleaching started (scale bar = 12.5 μm). (B) Analysis of fluorescence decay in the 25 μm segment in proximal dendrite. No significant difference was observed in fluorescence decay under the external electric-field application, suggesting that the electric field does not influence GluR1-GFP movement, directly (n = 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 10: An externally applied electric field does not influence the movement of GluR1-GFP. (A) GluR1-GFP was expressed in hippocampal dissociated culture neurons by a Sindbis virus expression system. The images were taken every 10 s. After taking 10 baseline images, a region that included the soma and the distal dendrites (green boxes) was photobleached, leaving a 25 μm length segment in proximal dendrite. Then, the photobleaching was repeated after every 5 images acquired. For the experiments with the electric-field application, a 10 mV/mm of external electric field was continuously applied along the primary dendrites once the photobleaching started (scale bar = 12.5 μm). (B) Analysis of fluorescence decay in the 25 μm segment in proximal dendrite. No significant difference was observed in fluorescence decay under the external electric-field application, suggesting that the electric field does not influence GluR1-GFP movement, directly (n = 5).
Mentions: If a dendritic electric field generated by a voltage gradient along the dendritic axis regulates GluR1 distribution, then an externally applied electric field might be able to similarly alter GluR1 distribution. We tested this hypothesis by applying a chronic electric field, parallel to the main apical dendritic axis, to hippocampal slices (Figure 8B; see Materials and Methods for detail) and then measuring GluR1 distribution using immunohistochemical techniques. The field was applied for 4 h, with the somatic region representing either the positive or negative pole. Following chronic field stimulation, we found that GluR1 distribution was significantly influenced in a direction-sensitive manner (signal ratio of s. pyramidale to s. radiatum: soma positive 0.76 ± 0.06, soma negative 1.05 ± 0.08; Figure 8C). Corresponding to the GluR1 distribution, we found that mEPSC frequency was also significantly influenced by an external electric field-application in a direction-sensitive manner (mEPSC amplitude: soma positive 12.01 ± 0.40 pA, soma negative 12.52 ± 0.29 pA; mEPSC frequency: soma positive 0.83 ± 0.09 Hz, soma positive 1.15 ± 0.07 Hz; Figure 9). Furthermore, this differential electric-field induced change in GluR1 distribution was completely abolished by the addition of a protein-synthesis inhibitor, anisomycin (soma positive: 0.82 ± 0.07, soma negative: 0.78 ± 0.06; Figure 8D). Fluorescence-loss-in-photobleaching experiments in neurons expressing a GluR1-GFP fusion protein argue against a direct effect of electric field on GluR1 movement (Figure 10). These results show that a modest change in the electric field along the dendritic axis is sufficient to elicit a protein-synthesis dependent change in the distribution of GluR1.

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