Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes Research Center, Atlanta, GA, USA.
J Physiol. 2012 Oct 1;590(19):4819-38. doi: 10.1113/jphysiol.2012.237453. Epub 2012 Jul 30.
The basolateral amygdala (BLA) is critically involved in the pathophysiology of psychiatric disorders, which often emerge during brain development. Several studies have characterized postnatal changes to the morphology and biochemistry of BLA neurons, and many more have identified sensitive periods of emotional maturation. However, it is impossible to determine how BLA development contributes to emotional development or the aetiology of psychiatric disorders because no study has characterized the physiological maturation of BLA neurons. We addressed this critical knowledge gap for the first time using whole-cell patch clamp recording in rat BLA principal neurons to measure electrophysiological properties at postnatal day (P)7, P10, P14, P21, P28 and after P35. We show that intrinsic properties of these neurons undergo significant transitions before P21 and reach maturity around P28. Specifically, we observed significant reductions in input resistance and membrane time constant of nearly 10-and 4-fold, respectively, from P7 to P28. The frequency selectivity of these neurons to input also changed significantly, with peak resonance frequency increasing from 1.0 Hz at P7 to 5.7 Hz at P28. In the same period, maximal firing frequency significantly increased and doublets and triplets of action potentials emerged. Concomitantly, individual action potentials became significantly faster, firing threshold hyperpolarized 6.7 mV, the medium AHP became faster and shallower, and a fast AHP emerged. These results demonstrate neurons of the BLA undergo vast change throughout postnatal development, and studies of emotional development and treatments for juvenile psychiatric disorders should consider the dynamic physiology of the immature BLA.
基底外侧杏仁核 (BLA) 在精神疾病的病理生理学中起着至关重要的作用,而这些疾病通常在大脑发育期间出现。几项研究已经描述了 BLA 神经元在形态和生物化学方面的产后变化,更多的研究已经确定了情绪成熟的敏感时期。然而,由于没有研究描述 BLA 神经元的生理成熟,因此无法确定 BLA 发育如何促进情绪发育或精神疾病的病因。我们首次使用大鼠 BLA 主神经元的全细胞膜片钳记录来解决这一关键的知识空白,以测量出生后第 7 天 (P7)、第 10 天 (P10)、第 14 天 (P14)、第 21 天 (P21)、第 28 天 (P28) 和 P35 后的电生理特性。我们表明,这些神经元的内在特性在 P21 之前发生了重大转变,并在 P28 左右达到成熟。具体来说,我们观察到从 P7 到 P28,输入电阻和膜时间常数分别显著降低了近 10 倍和 4 倍。这些神经元对输入的频率选择性也发生了显著变化,峰值共振频率从 P7 的 1.0 Hz 增加到 P28 的 5.7 Hz。在此期间,最大放电频率显著增加,出现了双脉冲和三脉冲动作电位。同时,单个动作电位变得明显更快,放电阈值超极化 6.7 mV,中等 AHP 变得更快且更浅,快速 AHP 出现。这些结果表明 BLA 中的神经元在整个产后发育过程中发生了巨大变化,而对青少年精神疾病的情绪发育和治疗的研究应该考虑到未成熟 BLA 的动态生理学。