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Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

Pashut T, Magidov D, Ben-Porat H, Wolfus S, Friedman A, Perel E, Lavidor M, Bar-Gad I, Yeshurun Y, Korngreen A - Front Cell Neurosci (2014)

Bottom Line: Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood.In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field.Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

View Article: PubMed Central - PubMed

Affiliation: The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University Ramat-Gan, Israel.

ABSTRACT
Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

No MeSH data available.


Related in: MedlinePlus

The magnetic threshold was correlated with intrinsic cellular properties. (A) The magnetic threshold of L5 pyramidal neurons (green circles) and low threshold interneurons (blue circles) recorded in the loose-patch configuration are plotted as a function of the current threshold recorded in the whole-cell configuration. (B) The magnetic thresholds of the neurons presented in (A) are plotted as a function of the input resistance. (C) The magnetic threshold recorded from L5 pyramidal neurons plotted as a function of the surface area, measured from stained neurons using Neurolucida (filled circles). The simulated magnetic threshold was calculated by systematically modifying the membrane area of a compartmental model for an L5 pyramidal neuron, while randomly modifying the surface area of the dendritic tree (line). (D) The magnetic threshold obtained from L5 pyramidal neurons in slices, in which the synaptic activity had been increased by replacing ACSF with ACSF2, plotted as a function of the surface area measured with Nerolucida from stained neurons (filled circles). The line is the same as that presented in (C). (E) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF in the presence of blockers for synaptic transmission (APV, bicuculline, CNQX). (F) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF2.
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Figure 5: The magnetic threshold was correlated with intrinsic cellular properties. (A) The magnetic threshold of L5 pyramidal neurons (green circles) and low threshold interneurons (blue circles) recorded in the loose-patch configuration are plotted as a function of the current threshold recorded in the whole-cell configuration. (B) The magnetic thresholds of the neurons presented in (A) are plotted as a function of the input resistance. (C) The magnetic threshold recorded from L5 pyramidal neurons plotted as a function of the surface area, measured from stained neurons using Neurolucida (filled circles). The simulated magnetic threshold was calculated by systematically modifying the membrane area of a compartmental model for an L5 pyramidal neuron, while randomly modifying the surface area of the dendritic tree (line). (D) The magnetic threshold obtained from L5 pyramidal neurons in slices, in which the synaptic activity had been increased by replacing ACSF with ACSF2, plotted as a function of the surface area measured with Nerolucida from stained neurons (filled circles). The line is the same as that presented in (C). (E) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF in the presence of blockers for synaptic transmission (APV, bicuculline, CNQX). (F) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF2.

Mentions: To test these theoretical predictions experimentally we targeted two populations of neurons in the somatosensory cortex, L5 pyramidal neurons and low threshold interneurons. Input resistance and current threshold were recorded in the whole-cell configuration followed by magnetic threshold in the loose-patch configuration. As our simulations predicted, the current threshold displayed a statistically significant positive correlation with the magnetic threshold (R = 0.65, p < 0.05, Figure 5A), while the input resistance displayed a statistically significant negative correlation with the magnetic threshold (R = −0.9, p < 0.001, Figure 5B). In both cases there was clear clustering of the results recorded from L5 pyramidal neurons and low threshold interneurons (Figures 5A,B). We also predicted that the magnetic threshold would be correlated with the size of the somatic compartment (Pashut et al., 2011). To investigate this prediction the morphologies of a group of L5 pyramidal neurons were reconstructed using Neurolucida and the somatic surface area was calculated. The measured magnetic threshold was indeed correlated with the surface area of the somatic membrane (Figure 5C).


Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

Pashut T, Magidov D, Ben-Porat H, Wolfus S, Friedman A, Perel E, Lavidor M, Bar-Gad I, Yeshurun Y, Korngreen A - Front Cell Neurosci (2014)

The magnetic threshold was correlated with intrinsic cellular properties. (A) The magnetic threshold of L5 pyramidal neurons (green circles) and low threshold interneurons (blue circles) recorded in the loose-patch configuration are plotted as a function of the current threshold recorded in the whole-cell configuration. (B) The magnetic thresholds of the neurons presented in (A) are plotted as a function of the input resistance. (C) The magnetic threshold recorded from L5 pyramidal neurons plotted as a function of the surface area, measured from stained neurons using Neurolucida (filled circles). The simulated magnetic threshold was calculated by systematically modifying the membrane area of a compartmental model for an L5 pyramidal neuron, while randomly modifying the surface area of the dendritic tree (line). (D) The magnetic threshold obtained from L5 pyramidal neurons in slices, in which the synaptic activity had been increased by replacing ACSF with ACSF2, plotted as a function of the surface area measured with Nerolucida from stained neurons (filled circles). The line is the same as that presented in (C). (E) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF in the presence of blockers for synaptic transmission (APV, bicuculline, CNQX). (F) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: The magnetic threshold was correlated with intrinsic cellular properties. (A) The magnetic threshold of L5 pyramidal neurons (green circles) and low threshold interneurons (blue circles) recorded in the loose-patch configuration are plotted as a function of the current threshold recorded in the whole-cell configuration. (B) The magnetic thresholds of the neurons presented in (A) are plotted as a function of the input resistance. (C) The magnetic threshold recorded from L5 pyramidal neurons plotted as a function of the surface area, measured from stained neurons using Neurolucida (filled circles). The simulated magnetic threshold was calculated by systematically modifying the membrane area of a compartmental model for an L5 pyramidal neuron, while randomly modifying the surface area of the dendritic tree (line). (D) The magnetic threshold obtained from L5 pyramidal neurons in slices, in which the synaptic activity had been increased by replacing ACSF with ACSF2, plotted as a function of the surface area measured with Nerolucida from stained neurons (filled circles). The line is the same as that presented in (C). (E) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF in the presence of blockers for synaptic transmission (APV, bicuculline, CNQX). (F) Box plot of the latency between the magnetic stimulus and the action potential recorded when the brain slice was bathed in ACSF2.
Mentions: To test these theoretical predictions experimentally we targeted two populations of neurons in the somatosensory cortex, L5 pyramidal neurons and low threshold interneurons. Input resistance and current threshold were recorded in the whole-cell configuration followed by magnetic threshold in the loose-patch configuration. As our simulations predicted, the current threshold displayed a statistically significant positive correlation with the magnetic threshold (R = 0.65, p < 0.05, Figure 5A), while the input resistance displayed a statistically significant negative correlation with the magnetic threshold (R = −0.9, p < 0.001, Figure 5B). In both cases there was clear clustering of the results recorded from L5 pyramidal neurons and low threshold interneurons (Figures 5A,B). We also predicted that the magnetic threshold would be correlated with the size of the somatic compartment (Pashut et al., 2011). To investigate this prediction the morphologies of a group of L5 pyramidal neurons were reconstructed using Neurolucida and the somatic surface area was calculated. The measured magnetic threshold was indeed correlated with the surface area of the somatic membrane (Figure 5C).

Bottom Line: Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood.In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field.Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

View Article: PubMed Central - PubMed

Affiliation: The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University Ramat-Gan, Israel.

ABSTRACT
Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

No MeSH data available.


Related in: MedlinePlus