Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia 22908, USA.
Epilepsia. 2011 Mar;52(3):523-30. doi: 10.1111/j.1528-1167.2010.02919.x. Epub 2011 Jan 4.
The midline thalamus is an important component of the circuitry in limbic seizures, but it is unclear how synaptic modulation of the thalamus affects that circuitry. In this study, we wished to understand how synaptic modulation of the thalamus can affect interregional signaling and seizure spread in the limbic network.
We examined the effect of γ-aminobutyric acid (GABA) modulation of the mediodorsal (MD) region of the thalamus on responses in the prefrontal cortex (PFC) by stimulation of the subiculum (SB). Muscimol, a GABA(A) agonist, was injected into the MD, and the effect on local responses to subiculum stimulation was examined. Evoked potentials were induced in the MD and the PFC by low-frequency stimulation of the SB, and seizures were generated in the subiculum by repeated 20-Hz stimulations. The effect of muscimol in the MD on the evoked potentials and seizures was measured.
Thalamic responses to stimulation of the subiculum were reduced in the presence of muscimol. Reduction of the amplitudes of evoked potentials in the MD resulted in an attenuation of the late, thalamic components of the responses in the PFC, as well as of seizure durations.
Activation of GABA(A) receptors in the midline thalamus not only causes changes within the thalamus, but it has broader effects on the limbic network. This work provides further evidence that synaptic modulation within the midline thalamus alters system excitability more broadly and reduces seizure activity.
中脑丘脑是边缘性癫痫发作回路的重要组成部分，但丘脑的突触调节如何影响该回路尚不清楚。在这项研究中，我们希望了解丘脑的突触调节如何影响边缘网络中的区域间信号传递和癫痫发作传播。
我们通过刺激下托（subiculum，SB）来检查中脑背内侧区（mediodorsal，MD）的γ-氨基丁酸（GABA）调制对前额叶皮质（prefrontal cortex，PFC）反应的影响。将 GABA(A) 激动剂 muscimol 注射到 MD 中，然后检查对下托刺激的局部反应的影响。通过下托的低频刺激在 MD 和 PFC 中诱导诱发电位，并通过重复 20-Hz 刺激在下托中产生癫痫发作。测量 MD 中 muscimol 对诱发电位和癫痫发作的影响。
在下托刺激存在 muscimol 的情况下，丘脑对刺激的反应减少。MD 中诱发电位幅度的减小导致 PFC 中反应的晚期丘脑成分以及癫痫发作持续时间的衰减。
中线丘脑内 GABA(A) 受体的激活不仅会导致丘脑内的变化，而且会对边缘网络产生更广泛的影响。这项工作进一步证明，中线丘脑内的突触调节更广泛地改变了系统兴奋性，并减少了癫痫活动。
