Eccles Institute of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
J Neurophysiol. 2012 Nov;108(10):2810-8. doi: 10.1152/jn.00524.2012. Epub 2012 Sep 5.
GABA(B) receptors play a key role in regulating neuronal excitability in the brain. Whereas the impact of somatic GABA(B) receptors on neuronal excitability has been studied in some detail, much less is known about the role of dendritic GABA(B) receptors. Here, we investigate the impact of GABA(B) receptor activation on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat barrel cortex. Activation of GABA(B) receptors led to hyperpolarization and a decrease in membrane resistance that was greatest at somatic and proximal dendritic locations. These effects were occluded by low concentrations of barium (100 μM), suggesting that they are mediated by potassium channels. In contrast, activation of dendritic GABA(B) receptors decreased the width of backpropagating action potential (APs) and abolished dendritic calcium electrogenesis, indicating that dendritic GABA(B) receptors regulate excitability, primarily via inhibition of voltage-dependent calcium channels. These distinct actions of somatic and dendritic GABA(B) receptors regulated neuronal output in different ways. Activation of somatic GABA(B) receptors led to a reduction in neuronal output, primarily by increasing the AP rheobase, whereas activation of dendritic GABA(B) receptors blocked burst firing, decreasing AP output in the absence of a significant change in somatic membrane properties. Taken together, our results show that GABA(B) receptors regulate somatic and dendritic excitability of cortical pyramidal neurons via different cellular mechanisms. Somatic GABA(B) receptors activate potassium channels, leading primarily to a subtractive or shunting form of inhibition, whereas dendritic GABA(B) receptors inhibit dendritic calcium electrogenesis, leading to a reduction in bursting firing.
GABA(B) 受体在调节大脑神经元兴奋性方面发挥着关键作用。虽然已经对躯体 GABA(B) 受体对神经元兴奋性的影响进行了详细研究，但对树突 GABA(B) 受体的作用知之甚少。在这里，我们研究了 GABA(B) 受体激活对大鼠皮层桶状核层 5 型锥体神经元的体-树突兴奋性的影响。GABA(B) 受体的激活导致超极化和膜电阻降低，在躯体和近端树突位置最大。这些效应被低浓度钡（100 μM）阻断，表明它们是由钾通道介导的。相比之下，树突 GABA(B) 受体的激活减小了逆行动作电位 (AP) 的宽度并消除了树突钙电发生，表明树突 GABA(B) 受体通过抑制电压依赖性钙通道来调节兴奋性。躯体和树突 GABA(B) 受体的这些不同作用以不同的方式调节神经元输出。躯体 GABA(B) 受体的激活导致神经元输出减少，主要是通过增加 AP 电流阈值来实现，而树突 GABA(B) 受体的激活阻断爆发放电，在不显著改变躯体膜特性的情况下减少 AP 输出。总之，我们的结果表明，GABA(B) 受体通过不同的细胞机制调节皮质锥体神经元的体-树突兴奋性。躯体 GABA(B) 受体激活钾通道，主要导致减法或分流抑制形式，而树突 GABA(B) 受体抑制树突钙电发生，导致爆发放电减少。
