Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Centre, Sanger Hall, 1101 E. Marshall St, Richmond, VA 23298, USA.
J Physiol. 2011 Feb 15;589(Pt 4):919-37. doi: 10.1113/jphysiol.2010.202499. Epub 2010 Dec 20.
In developing cells of the mouse dorsal lateral geniculate nucleus (dLGN), synaptic responses evoked by optic tract (OT) stimulation give rise to long-lasting, high-amplitude depolarizations known as plateau potentials. These events are mediated by L-type Ca2+ channels and occur during early postnatal life, a time when retinogeniculate connections are remodelling. To better understand the relationship between L-type activity and dLGN development we used an in vitro thalamic slice preparation which preserves the retinal connections and intrinsic circuitry in dLGN and examined how synaptic responses evoked by OT stimulation lead to the activation of plateau potentials. By varying the strength and temporal frequency of OT stimulation we identified at least three factors that contribute to the developmental regulation of plateau activity: the degree of retinal convergence, the temporal pattern of retinal stimulation and the emergence of feed-forward inhibition. Before natural eye opening (postnatal day 14), the excitatory synaptic responses of relay cells receiving multiple retinal inputs summated in both the spatial and temporal domains to produce depolarizations sufficient to activate L-type activity. After eye opening, when inhibitory responses are fully developed, plateau activity was rarely evoked even with high temporal rates of OT stimulation. When the bulk of this inhibition was blocked by bath application of bicuculline, the incidence of plateau activity increased significantly. We also made use of a transgenic mouse that lacks the β3 subunit of the L-type Ca2+ channel. These mutants have far fewer membrane-bound Ca2+ channels and attenuated L-type activity. In β3 nulls, L-type plateau activity was rarely observed even at young ages when plateau activity prevails. Thus, in addition to the changing patterns of synaptic connectivity and retinal activity, the expression of L-type Ca2+ channels is a requisite component in the manifestation of plateau activity.
在小鼠背外侧膝状体核 (dLGN) 的发育细胞中，由视束 (OT) 刺激引发的突触反应产生长时程、高幅度去极化，称为平台电位。这些事件是由 L 型 Ca2+ 通道介导的，发生在出生后的早期，此时视网膜-膝状体连接正在重塑。为了更好地理解 L 型活性与 dLGN 发育之间的关系，我们使用了一种体外丘脑切片制备方法，该方法保留了视网膜连接和 dLGN 中的内在电路，并研究了 OT 刺激引发的突触反应如何导致平台电位的激活。通过改变 OT 刺激的强度和时间频率，我们确定了至少有三个因素有助于调节平台活动的发育：视网膜会聚的程度、视网膜刺激的时间模式和前馈抑制的出现。在自然睁眼（出生后第 14 天）之前，接受多个视网膜输入的中继细胞的兴奋性突触反应在空间和时间域中总和，产生足以激活 L 型活性的去极化。在睁眼后，当抑制性反应完全发育时，即使在 OT 刺激的高时间频率下，也很少引发平台活动。当使用浴中应用 Bicuculline 阻断大部分这种抑制时，平台活动的发生率显著增加。我们还利用一种缺乏 L 型 Ca2+ 通道的β3 亚基的转基因小鼠。这些突变体的膜结合 Ca2+ 通道少得多，L 型活性减弱。在β3 缺失突变体中，即使在平台活动盛行的年轻时期，也很少观察到 L 型平台活动。因此，除了突触连接和视网膜活动的变化模式外，L 型 Ca2+ 通道的表达也是平台活动表现的必需组成部分。
