Mechanism of regulation of neuronal activity in the basolateral amygdala by medial prefrontal cortex

为了研究去甲肾上腺素（NA）对中大型gabaergy神经元的影响，并鉴定gabaergy神经元活性受内侧前额叶皮层投射调节的细胞类型，我们制备了谷氨酸脱羧酶67 (GAD67)-绿色荧光蛋白（GFP）敲入小鼠，GFP在gabaergy神经元中特异性表达。利用全细胞膜片钳体外记录，根据去极化电流诱导的动作电位放电模式，在BLA中鉴定出三种不同电生理类型的gaba能神经元：a型规则尖峰（RS）细胞、b型低阈尖峰（LTS）细胞和c型快速尖峰（FS）细胞。三种gaba能神经元的电生理特性也存在差异。我们发现NA通过α_1-肾上腺素受体优先激活A-RS型细胞并增强强直抑制，而对其他类型神经元的影响最小。净na诱导电流的平均反转电位为-31.3±7.6 mV。将外部Na^+浓度降低到27 mM时，逆转电位向负值移动，并显示出额外的逆转电位。这些结果表明，NA的作用是通过激活非选择性阳离子电导和抑制静息K^+电导介导的，NA对BLA神经活动的影响是通过刺激特定的gaba能中间神经元亚群介导的gaba能抑制的增强。此外，绝大多数A型细胞接受来自内侧前额叶皮层（XX/YY）的单突触输入，而B型（XX/YY）和C型（XX/YY）细胞接受单突触输入的频率较低，这表明A型细胞在内侧前额叶皮层前馈抑制BLA活性方面发挥了主要作用

To investigate the noradrenaline (NA) effects on medium-to large-sized GABAergic neurons, and also to identify the GABAergic cell types whose activity are regulated by projection from medial prefrontal cortex, we generated glutamate decarboxylase 67 (GAD67)-green fluorescent protein (GFP) knock-in mice, in which GFP was specifically expressed in GABAergic neurons. Using whole-cell patch-clamp recordings in vitro, three electrophysiologically distinct types of GABAergic neurons were identified in the BLA on the basis of the action potential firing pattern induced by depolarizing current injection : Type A-regular spiking (RS) cells, Type B-low threshold spiking (LTS), cells and Type C-fastspiking (FS) cells. Electrophysiological properties also showed difference among these three types of GABAergic neurons. We found that NA preferentially excited Type A-RS cells via α_1-adrenoceptors and augmented tonic inhibition while minimally affecting the other types of neurons. Averaged reversal potential of the net NA-induced, current was -31.3 ± 7.6 mV. Reducing the external Na^+ concentration to 27 mM shifted the reversal potential to more negative values and also revealed an additional reversal potential. These results indicate that the NA effect was, mediated by activation of nonselective cationic conductance and suppression of the resting K^+ conductance and that the NA effect on the neural activity of the BLA involves augmentation of GABAergic inhibition mediated by exciting a specific subpopulation of GABAergic interneurons. In addition, great majority of Type A cells receive monosynaptic input from medial prefrontal cortex (XX/YY), whereas Type B (XX/YY) and Type C (XX/YY) cells do it less frequently, suggesting a major role for Type A cells in feedforward inhibition of the activity in the BLA by medial prefrontal cortex