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 Ca2+ 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

A quantitative method for determining spatial discriminative capacity

Abstract Background The traditional two-point discrimination (TPD) test, a widely used tactile spatial acuity measure, has been criticized as being imprecise because it is based on subjective criteria and involves a number of non-spatial cues. The results of a recent study showed that as two stimuli were delivered simultaneously, vibrotactile amplitude discrimination became worse when the two stimuli were positioned relatively close together and was significantly degraded when the probes were within a subject's two-point limen. The impairment of amplitude discrimination with decreasing inter-probe distance suggested that the metric of amplitude discrimination could possibly provide a means of objective and quantitative measurement of spatial discrimination capacity. Methods A two alternative forced-choice (2AFC) tracking procedure was used to assess a subject's ability to discriminate the amplitude difference between two stimuli positioned at near-adjacent skin sites. Two 25 Hz flutter stimuli, identical except for a constant difference in amplitude, were delivered simultaneously to the hand dorsum. The stimuli were initially spaced 30 mm apart, and the inter-stimulus distance was modified on a trial-by-trial basis based on the subject's performance of discriminating the stimulus with higher intensity. The experiment was repeated via sequential, rather than simultaneous, delivery of the same vibrotactile stimuli. Results Results obtained from this study showed that the performance of the amplitude discrimination task was significantly degraded when the stimuli were delivered simultaneously and were near a subject's two-point limen. In contrast, subjects were able to correctly discriminate between the amplitudes of the two stimuli when they were sequentially delivered at all inter-probe distances (including those within the two-point limen), and improved when an adapting stimulus was delivered prior to simultaneously delivered stimuli. Conclusion Subjects' capacity to discriminate the amplitude difference between two vibrotactile stimulations was degraded as the inter-stimulus distance approached the limit of their two-point spatial discriminative capacity. This degradation of spatial discriminative capacity lessened when an adapting stimulus was used. Performance of the task, as well as improvement on the task with adaptation, would most likely be impaired if the cortical information processing capacity of a subject or subject population were systemically altered, and thus, the methods described could be effective measures for use in clinical or clinical research applications

Continuous theta-burst stimulation modulates tactile synchronization

Abstract Background Temporal order judgement (TOJ) is the ability to detect the order of occurrence of two sequentially delivered stimuli. Previous research has shown that TOJ in the presence of synchronized periodic conditioning stimuli impairs TOJ performance, and this phenomenon is suggested to be mediated by GABAergic interneurons that cause perceptual binding across the two skin sites. Application of continuous theta-burst repetitive TMS (cTBS) over primary somatosensory cortex (SI) alters temporal and spatial tactile perception. The purpose of this study was to examine TOJ perception in the presence and absence of synchronized periodic conditioning stimuli before and after cTBS applied over left-hemisphere SI. A TOJ task was administered on the right index and middle finger (D2 and D3) in two separate sessions in the presence and absence of conditioning stimuli (a background low amplitude sinusoidal vibration). Results CTBS reduced the impact of the conditioning stimuli on TOJ performance for up to 18 minutes following stimulation while sham cTBS did not affect TOJ performance. In contrast, the TOJ task performed in the absence of synchronized conditioning stimulation was unaltered following cTBS. Conclusion We conclude that cTBS suppresses inhibitory networks in SI that mediate perceptual binding during TOJ synchronization. CTBS offers one method to suppress cortical excitability in the cortex and potentially benefit clinical populations with altered inhibitory cortical circuits. Additionally, TOJ measures with conditioning stimuli may provide an avenue to assess sensory processing in neurologically impaired patient populations