Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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<sup>-</sup>]<sub>i</sub> after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABA<sub>A</sub> receptors agonist, was applied right after stimulation while monitoring the intracellular Ca<sup>2+</sup> concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca<sup>2+</sup>]<sub>i</sub> in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca<sup>2+</sup> signal showed a column-shaped distribution along the stimulation site.</p> <p>Conclusion</p> <p>These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.</p>
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