Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Eur J Neurosci. 2013 Aug;38(4):2542-56. doi: 10.1111/ejn.12262. Epub 2013 Jun 3.
The subiculum, a para-hippocampal structure positioned between the cornu ammonis 1 subfield and the entorhinal cortex, has been implicated in temporal lobe epilepsy in human patients and in animal models of epilepsy. The structure is characterized by the presence of a significant population of burst firing neurons that has been shown previously to lead epileptiform activity locally. Phase transitions in epileptiform activity in neurons following a prolonged challenge with an epileptogenic stimulus has been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of phase transitions in the burst firing neurons of the subiculum in an in vitro rat brain slice model of epileptogenesis. Whole-cell patch-clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable state was followed by a late suppressed state upon continuous perfusion with epileptogenic 4-aminopyridine and magnesium-free medium. The suppressed state was characterized by inhibitory post-synaptic potentials in pyramidal excitatory neurons and bursting activity in local fast-spiking interneurons at a frequency of 0.1-0.8 Hz. The inhibitory post-synaptic potentials were mediated by GABAA receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These inhibitory post-synaptic potentials ceased following a cut between the cornu ammonis 1 and subiculum. The suppression of epileptiform activity in the subiculum thus represents a homeostatic response towards the induced hyperexcitability. Our results suggest the importance of feedforward inhibition in exerting this homeostatic control.
下托（subiculum），一种位于角状回 1 区和内嗅皮层之间的海马旁结构，已被证明在人类癫痫患者和癫痫动物模型中与颞叶癫痫有关。该结构的特征是存在大量爆发放电神经元，先前已证明这些神经元会导致局部癫痫样活动。在其他脑结构中已经观察到在长时间受到致癫痫刺激后神经元的癫痫样活动中的相变，但在下托中尚未观察到。考虑到下托爆发放电神经元在将癫痫样活动传播到内嗅皮层中的重要性，我们在癫痫发生的体外大鼠脑片模型中探索了下托爆发放电神经元中相变的现象。全细胞膜片钳和细胞外场记录显示，在下托中存在一种明显的现象，即在持续用致癫痫的 4-氨基吡啶和无镁培养基灌注后，早期的超兴奋性状态随后是晚期的抑制性状态。抑制性状态的特征是在 0.1-0.8 Hz 的频率下，兴奋性锥体神经元中存在抑制性突触后电位和局部快速放电中间神经元中的爆发活动。抑制性突触后电位是由 GABAA 受体介导的，与兴奋性突触输入一致，以减弱动作电位放电。这些抑制性突触后电位在下托与角状回 1 区之间的切割后停止。因此，下托中癫痫样活动的抑制代表了对诱导的超兴奋性的一种自身平衡反应。我们的结果表明，前馈抑制在发挥这种自身平衡控制中的重要性。
