Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons

Jaekwang Lee; Junsung Woo; Oleg V. Favorov; Mark Tommerdahl; C. Justin Lee; Barry L. Whitsel

doi:10.1186/1756-6606-5-33

Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons

Jaekwang Lee, Junsung Woo, Oleg V. Favorov, Mark Tommerdahl, C. Justin Lee, Barry L. Whitsel

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background: GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Results: Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl^-]_i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABA_A receptors agonist, was applied right after stimulation while monitoring the intracellular Ca ²⁺ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca²⁺]_i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca²⁺ signal showed a column-shaped distribution along the stimulation site. Conclusion: These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.

Original language	English
Article number	33
Journal	Molecular brain
Volume	5
Issue number	1
DOIs	https://doi.org/10.1186/1756-6606-5-33
Publication status	Published - 2012

Bibliographical note

Funding Information:
The authors greatly thank Betsy Houston for expert technical assistance. The experiments reported in this paper were funded, in part, by National Institutes of Health RO1 grant (NS37501; B.L.W., P.I.) and Army Research Office grant (W911NF-08-1-0308; M. T., P.I.). Jaekwang Lee was supported, in part, by a fellowship provided by the predoctoral training program of the Department of Biomedical Engineering of the University of North Carolina School of Medicine. The authors thank Betsy Houston for expert technical assistance. The research described in this paper was carried out by J. Lee in partial fulfillment of the requirements for the Ph.D. degree in Biomedical Engineering at the University of North Carolina, School of Medicine, Chapel Hill, NC, USA.

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience

Access to Document

10.1186/1756-6606-5-33

Cite this

@article{73057c7c2800441996328c08584926c1,

title = "Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons",

abstract = "Background: GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Results: Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl-]i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABAA receptors agonist, was applied right after stimulation while monitoring the intracellular Ca 2+ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca2+]i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca2+ signal showed a column-shaped distribution along the stimulation site. Conclusion: These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.",

author = "Jaekwang Lee and Junsung Woo and Favorov, {Oleg V.} and Mark Tommerdahl and Lee, {C. Justin} and Whitsel, {Barry L.}",

note = "Funding Information: The authors greatly thank Betsy Houston for expert technical assistance. The experiments reported in this paper were funded, in part, by National Institutes of Health RO1 grant (NS37501; B.L.W., P.I.) and Army Research Office grant (W911NF-08-1-0308; M. T., P.I.). Jaekwang Lee was supported, in part, by a fellowship provided by the predoctoral training program of the Department of Biomedical Engineering of the University of North Carolina School of Medicine. The authors thank Betsy Houston for expert technical assistance. The research described in this paper was carried out by J. Lee in partial fulfillment of the requirements for the Ph.D. degree in Biomedical Engineering at the University of North Carolina, School of Medicine, Chapel Hill, NC, USA.",

year = "2012",

doi = "10.1186/1756-6606-5-33",

language = "English",

volume = "5",

journal = "Molecular brain",

issn = "1756-6606",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons

AU - Lee, Jaekwang

AU - Woo, Junsung

AU - Favorov, Oleg V.

AU - Tommerdahl, Mark

AU - Lee, C. Justin

AU - Whitsel, Barry L.

N1 - Funding Information: The authors greatly thank Betsy Houston for expert technical assistance. The experiments reported in this paper were funded, in part, by National Institutes of Health RO1 grant (NS37501; B.L.W., P.I.) and Army Research Office grant (W911NF-08-1-0308; M. T., P.I.). Jaekwang Lee was supported, in part, by a fellowship provided by the predoctoral training program of the Department of Biomedical Engineering of the University of North Carolina School of Medicine. The authors thank Betsy Houston for expert technical assistance. The research described in this paper was carried out by J. Lee in partial fulfillment of the requirements for the Ph.D. degree in Biomedical Engineering at the University of North Carolina, School of Medicine, Chapel Hill, NC, USA.

PY - 2012

Y1 - 2012

N2 - Background: GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Results: Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl-]i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABAA receptors agonist, was applied right after stimulation while monitoring the intracellular Ca 2+ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca2+]i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca2+ signal showed a column-shaped distribution along the stimulation site. Conclusion: These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.

AB - Background: GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Results: Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl-]i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABAA receptors agonist, was applied right after stimulation while monitoring the intracellular Ca 2+ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca2+]i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca2+ signal showed a column-shaped distribution along the stimulation site. Conclusion: These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.

UR - http://www.scopus.com/inward/record.url?scp=84866494952&partnerID=8YFLogxK

U2 - 10.1186/1756-6606-5-33

DO - 10.1186/1756-6606-5-33

M3 - Article

C2 - 23006518

AN - SCOPUS:84866494952

SN - 1756-6606

VL - 5

JO - Molecular brain

JF - Molecular brain

IS - 1

M1 - 33

ER -

Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this