Pérez-Garci Enrique, Gassmann Martin, Bettler Bernhard, Larkum Matthew E
Institute of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland.
Neuron. 2006 May 18;50(4):603-16. doi: 10.1016/j.neuron.2006.04.019.
The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs with unknown functions. Here, we studied the functional consequences and underlying molecular mechanisms of apical inhibition on dendritic spike activity. Extracellular stimulation of layer 1, during blockade of glutamatergic transmission, inhibited the dendritic Ca2+ spike for up to 400 ms. Activation of metabotropic GABAB receptors was responsible for a gradual and long-lasting inhibitory effect, whereas GABAA receptors mediated a short-lasting (approximately 150 ms) inhibition. Our results suggest that the mechanism underlying the GABAB inhibition of Ca2+ spikes involves direct blockade of dendritic Ca2+ channels. By using knockout mice for the two predominant GABAB1 isoforms, GABAB1a and GABAB1b, we showed that postsynaptic inhibition of Ca2+ spikes is mediated by GABAB1b, whereas presynaptic inhibition of GABA release is mediated by GABAB1a. We conclude that the molecular subtypes of GABAB receptors play strategically different physiological roles in neocortical neurons.
第5层锥体神经元的顶端簇被大量功能未知的抑制性输入所支配。在这里，我们研究了顶端抑制对树突棘突活动的功能后果及潜在分子机制。在谷氨酸能传递被阻断期间，对第1层进行细胞外刺激，可抑制树突Ca2+棘突长达400毫秒。代谢型GABAB受体的激活导致了一种逐渐且持久的抑制作用，而GABAA受体介导了一种短暂（约150毫秒）的抑制作用。我们的结果表明，GABAB对Ca2+棘突抑制作用的潜在机制涉及对树突Ca2+通道的直接阻断。通过使用两种主要的GABAB1亚型GABAB1a和GABAB1b的基因敲除小鼠，我们发现对Ca2+棘突的突触后抑制由GABAB1b介导，而对GABA释放的突触前抑制由GABAB1a介导。我们得出结论，GABAB受体的分子亚型在新皮层神经元中发挥着策略性不同的生理作用。
