Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
Front Neural Circuits. 2012 May 31;6:33. doi: 10.3389/fncir.2012.00033. eCollection 2012.
Postnatal inhibitory neuron development affects mammalian brain function, and failure of this maturation process may underlie pathological conditions such as epilepsy, schizophrenia, and depression. Furthermore, understanding how physiological properties of inhibitory neurons change throughout development is critical to understanding the role(s) these cells play in cortical processing. One subset of inhibitory neurons that may be affected during postnatal development is somatostatin-expressing (SOM) cells. A subset of these cells is labeled with green-fluorescent protein (GFP) in a line of mice known as the GFP-positive inhibitory neurons (GIN) line. Here, we studied how intrinsic electrophysiological properties of these cells changed in the somatosensory cortex of GIN mice between postnatal ages P11 and P32+. GIN cells were targeted for whole-cell current-clamp recordings and ranges of positive and negative current steps were presented to each cell. The results showed that as the neocortical circuitry matured during this critical time period multiple intrinsic and firing properties of GIN inhibitory neurons, as well as those of excitatory (regular-spiking [RS]) cells, were altered. Furthermore, these changes were such that the output of GIN cells, but not RS cells, increased over this developmental period. We quantified changes in excitability by examining the input-output relationship of both GIN and RS cells. We found that the firing frequency of GIN cells increased with age, while the rheobase current remained constant across development. This created a multiplicative increase in the input-output relationship of the GIN cells, leading to increases in gain with age. The input-output relationship of the RS cells, on the other hand, showed primarily a subtractive shift with age, but no substantial change in gain. These results suggest that as the neocortex matures, inhibition coming from GIN cells may become more influential in the circuit and play a greater role in the modulation of neocortical activity.
出生后抑制性神经元的发育会影响哺乳动物的大脑功能，而这一成熟过程的失败可能是癫痫、精神分裂症和抑郁症等病理状况的基础。此外，了解抑制性神经元的生理特性如何在整个发育过程中发生变化，对于理解这些细胞在皮质处理中的作用至关重要。在出生后发育过程中可能受到影响的抑制性神经元亚群之一是生长抑素表达（SOM）细胞。在一种被称为 GFP 阳性抑制神经元（GIN）系的小鼠中，其中一部分细胞用绿色荧光蛋白（GFP）标记。在这里，我们研究了 GIN 小鼠在出生后 11 天至 32 天之间，其感觉皮层中这些细胞的内在电生理特性如何发生变化。对 GIN 细胞进行全细胞电流钳记录，并向每个细胞施加正、负电流阶跃。结果表明，在这段关键时期，新皮层回路成熟时，GIN 抑制性神经元以及兴奋性（规则放电 [RS]）神经元的多种内在和放电特性都发生了改变。此外，这些变化使得 GIN 细胞的输出，而不是 RS 细胞的输出，在这段发育期间增加。我们通过检查 GIN 和 RS 细胞的输入-输出关系来量化兴奋性的变化。我们发现，GIN 细胞的放电频率随着年龄的增长而增加，而在整个发育过程中，基强度电流保持不变。这导致 GIN 细胞的输入-输出关系呈乘法增加，从而导致随着年龄的增长增益增加。RS 细胞的输入-输出关系则主要表现为随年龄的增长而出现减法变化，但增益没有实质性变化。这些结果表明，随着新皮层的成熟，来自 GIN 细胞的抑制作用可能在回路中变得更加重要，并在调节新皮层活动中发挥更大的作用。
