We investigated the effects of muscimol on generation of spike-wave discharges (SWDs) and shortterm plasticity alterations in the somatosensory cortex of WAG/Rij rats. The rats were implanted with a twisted tripolar electrode into the somatosensory cortex and with an intraventricular cannula into the right cerebral ventricle. EEG recordings were made before and after muscimol and saline injections. Paired-pulse stimulations (200 μsec, 100-1000 μA, 0.1 sec–1) were applied to the somatosensory cortex at 50-, 100-, 400-, and 500-msec-long intervals for 50 min. Pharmacological amplification of GABAergic transmission in the somatosensory cortex exerted an inhibitory effect on the thalamo-cortical circuit underlying the generation of spike-wave discharges (SWDs). Ten minutes post-injection of muscimol, paired-pulse facilitation was significantly reduced at 50- and 100-msec-long interpulse intervals (P < 0.05). The data obtained suggest that muscimol suppresses generation of SWDs and changes short-term plasticity via imitation of the effects of GABA in inhibitory synapses.
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References
O. C. Snead, “Basic mechanisms of generalized absence seizures,” Ann. Neurol., 37, No. 2, 146-157 (1995).
G. D’Arcangelo, M. D’Antuono, G. Biagini, et al., “Thalamocortical oscillations in a genetic model of absence seizures,” Eur. J. Neurosci., 16, No. 12, 2383-2393 (2002).
E. van Luijtelaar and A. Coenen, “Two types of electrocortical paroxysms in an inbred strain of rats,” Neurosci. Lett., 70, No. 3, 393-397 (1986).
G. van Luijtelaar and E. Sitnikova, “Global and focal aspects of absence epilepsy: the contribution of genetic models,” Neurosci. Biobehav. Rev., 30, No. 7, 983-1003 (2006).
A. Lüttjohann, S. Zhang, R. de Peijper, and G. van Luijtelaar, “Electrical stimulation of the epileptic focus in absence epileptic WAG/Rij rats: assessment of local and network excitability,” Neuroscience, 188, 125-134 (2011).
A. M. L. Coenen and E. van Luijtelaar, “The WAG/Rij rat model for absence epilepsy: age and sex factors,” Epilepsy Res., 1, No. 5, 297-301 (1987).
L. Parsaei, M. Rangchiyan, S. Ahmadi, and M. R. Zarrindast, “GABAA receptors in the dorsal hippocampus are involved in sate-dependent learning induced by lithium in mice,” Iran J. Pharm. Res., 10, No. 1, 127 (2011).
M. Tian and R. L. Macdonald, “The intronic GABRG2 mutation, IVS6+ 2T→ G, associated with childhood absence epilepsy altered subunit mRNA intron splicing, activated nonsense-mediated decay, and produced a stable truncated γ2 subunit,” J. Neurosci., 32, No. 17, 5937-5952 (2012).
C. A. Reid and D. M. Kullmann, “GABA A receptor mutations in epilepsy (Commentary on Lachance, Touchette, et al.),” Eur. J. Neurosci., 34, No. 2, 235, (2011).
H. P. Goodkin, C. Sun, J. L. Yeh, et al., “GABA A receptor internalization during seizures,” Epilepsia, 48, s5, 109-113 (2007).
D. Debanne, N. C. Guerineau, B. Gähwiler, and S. M. Thompson, “Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release,” J. Physiol., 491, No. 1, 163-176 (1996).
C. F. Stevens and Y. Wang, “Facilitation and depression at single central synapses,” Neuron, 14, No. 4, 795-802 (1995).
M. A. Castro-Alamancos and B. W. Connors, “Cellular mechanisms of the augmenting response: short-term plasti-city in a thalamocortical pathway,” J. Neurosci., 16, No. 23, 7742-7756 (1996).
Z. Ataie, S. Babri, M. G. Golzar, et al., “GABA B receptor blockade prevents antiepileptic action of ghrelin in the rat hippocampus,” Adv. Pharm. Bull., 3, No. 2, 353 (2013).
G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition, Acad. Press (2006).
T. Baum and F. Becker, “Hypotensive and postural effects of the [gamma]-aminobutyric acid agonist muscimol and of clonidine,” J. Cardiovascul. Pharmacol., 4, No. 2, 165-159 (1982).
Y. Ma and D. A. Prince, “Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex,” Neurobiol. Dis., 47, No. 1, 102-113 (2012).
A. Depaulis, M. Vergnes, C. Marescaux, et al., “Evidence that activation of GABA receptors in the substantia nigra suppresses spontaneous spike-and-wave discharges in the rat,” Brain Res., 448, No. 1, 20-29 (1988).
J. C. Mulley, I. E. Scheffer, S. Petrou, and S. F. Berkovic, “Channelopathies as a genetic cause of epilepsy,” Current Opin. Neurol., 16, No. 2, 171-176 (2003).
H. K. Meeren, J. G. Veening, T. A. Möderscheim, et al., “Thalamic lesions in a genetic rat model of absence epilepsy: dissociation between spike-wave discharges and sleep spindles,” Exp. Neurol., 217, No. 1, 25-37(2009).
D. Merlo, C. Mollinari, Y. Inaba, et al., “Reduced GABA B receptor subunit expression and paired-pulse depression in a genetic model of absence seizures,” Neurobiol. Dis., 25, No. 3, 631-641 (2007).
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Nejad, G.G., Vastyanov, R.S., Shahabi, P. et al. Abnormalities in the GABAergic Inhibitory System Leading to the Development of Spike-Wave Discharges in the Somatosensory Cortex of Wag/Rij Rats. Neurophysiology 47, 454–458 (2015). https://doi.org/10.1007/s11062-016-9555-0
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DOI: https://doi.org/10.1007/s11062-016-9555-0