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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

Patch-clamp and magnetic stimulation setup. (A) The general configuration of the modified patch-clamp setup used for patching. The coil was concentric to the light path and the condenser was elevated to allow focusing the light on the brain slice. The Z-axis distance of the coil was set at 2 mm from the plane of the slice and the Y-axis location centered with respect to the center of the coil, while the coil location in the X-axis remained flexible. (B) The configuration of the patch-clamp setup used for during recording. The coil was moved laterally by 1 cm to allow optimal stimulation and the condenser was lowered to reduce mechanical interactions with the coil. (C) An image of the setup with the specimen stage removed, allowing visualization of the shielded coil and the manual manipulator for positioning the coil. (D) An image of the setup with the clear plastic table with a chamber for the brain slices in the middle. The electrode headstage can be seen on the left.
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Figure 1: Patch-clamp and magnetic stimulation setup. (A) The general configuration of the modified patch-clamp setup used for patching. The coil was concentric to the light path and the condenser was elevated to allow focusing the light on the brain slice. The Z-axis distance of the coil was set at 2 mm from the plane of the slice and the Y-axis location centered with respect to the center of the coil, while the coil location in the X-axis remained flexible. (B) The configuration of the patch-clamp setup used for during recording. The coil was moved laterally by 1 cm to allow optimal stimulation and the condenser was lowered to reduce mechanical interactions with the coil. (C) An image of the setup with the specimen stage removed, allowing visualization of the shielded coil and the manual manipulator for positioning the coil. (D) An image of the setup with the clear plastic table with a chamber for the brain slices in the middle. The electrode headstage can be seen on the left.

Mentions: A patch-clamp setup was modified to allow magnetic stimulation of cortical brain slices. Since the standard brain slice setup employs a water immersion objective it was not possible to place the magnetic coil above the brain slice. The coil was thus positioned between the condenser and the specimen table (Figure 1A). The proximity of the coil to the metal specimen table and the metal condenser induced eddy currents in these metal components, which reduced the magnetic pulse efficiency and introduced electrical noise and mechanical vibration during magnetic stimulation. To minimize the electrical artifacts we shielded the coil with a heavily grounded copper plate to reduce the radius of eddy current loops (Figure 1C). The metal stage of the microscope was replaced with a plastic one (Figure 1D), but it was not possible to replace the metal condenser. Thus, once a stable recording was established, the condenser was lowered for the duration of the experiment (Figure 1B). This greatly reduced the mechanical vibrations experienced during the magnetic pulse, except for high pulse intensities.


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)

Patch-clamp and magnetic stimulation setup. (A) The general configuration of the modified patch-clamp setup used for patching. The coil was concentric to the light path and the condenser was elevated to allow focusing the light on the brain slice. The Z-axis distance of the coil was set at 2 mm from the plane of the slice and the Y-axis location centered with respect to the center of the coil, while the coil location in the X-axis remained flexible. (B) The configuration of the patch-clamp setup used for during recording. The coil was moved laterally by 1 cm to allow optimal stimulation and the condenser was lowered to reduce mechanical interactions with the coil. (C) An image of the setup with the specimen stage removed, allowing visualization of the shielded coil and the manual manipulator for positioning the coil. (D) An image of the setup with the clear plastic table with a chamber for the brain slices in the middle. The electrode headstage can be seen on the left.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042461&req=5

Figure 1: Patch-clamp and magnetic stimulation setup. (A) The general configuration of the modified patch-clamp setup used for patching. The coil was concentric to the light path and the condenser was elevated to allow focusing the light on the brain slice. The Z-axis distance of the coil was set at 2 mm from the plane of the slice and the Y-axis location centered with respect to the center of the coil, while the coil location in the X-axis remained flexible. (B) The configuration of the patch-clamp setup used for during recording. The coil was moved laterally by 1 cm to allow optimal stimulation and the condenser was lowered to reduce mechanical interactions with the coil. (C) An image of the setup with the specimen stage removed, allowing visualization of the shielded coil and the manual manipulator for positioning the coil. (D) An image of the setup with the clear plastic table with a chamber for the brain slices in the middle. The electrode headstage can be seen on the left.
Mentions: A patch-clamp setup was modified to allow magnetic stimulation of cortical brain slices. Since the standard brain slice setup employs a water immersion objective it was not possible to place the magnetic coil above the brain slice. The coil was thus positioned between the condenser and the specimen table (Figure 1A). The proximity of the coil to the metal specimen table and the metal condenser induced eddy currents in these metal components, which reduced the magnetic pulse efficiency and introduced electrical noise and mechanical vibration during magnetic stimulation. To minimize the electrical artifacts we shielded the coil with a heavily grounded copper plate to reduce the radius of eddy current loops (Figure 1C). The metal stage of the microscope was replaced with a plastic one (Figure 1D), but it was not possible to replace the metal condenser. Thus, once a stable recording was established, the condenser was lowered for the duration of the experiment (Figure 1B). This greatly reduced the mechanical vibrations experienced during the magnetic pulse, except for high pulse intensities.

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