Konstantoudaki Xanthippi, Chalkiadaki Kleanthi, Vasileiou Elisabeth, Kalemaki Katerina, Karagogeos Domna, Sidiropoulou Kyriaki
Department of Biology, University of Crete , Heraklion , Greece.
Division of Basic Sciences, Faculty of Medicine, University of Crete , Heraklion , Greece.
J Neurophysiol. 2018 Mar 1;119(3):822-833. doi: 10.1152/jn.00189.2017. Epub 2017 Nov 22.
Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty-seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC, particularly compared with other primary cortical areas. This study aims to understand the development of PFC-mediated, compared with non-PFC-mediated, cognitive functions. Toward this aim, we performed cognitive behavioral tasks in adolescent and adult mice and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared with adult mice, whereas their performance in non-PFC-dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper-layer synapses of the PFC but not the barrel cortex. Blocking GABA receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the N-methyl-d-aspartate receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents. NEW & NOTEWORTHY This study reports that adolescent mice exhibit impaired performance in cognitive functions dependent on the prefrontal cortex but not in cognitive functions dependent on other cortical regions. The current results propose reduced synaptic plasticity in the upper layers of the prefrontal cortex as a cellular correlate of this weakened cognitive function. This decreased synaptic plasticity is due to reduced N-methyl-d-aspartate receptor expression but not due to dampened intrinsic excitability or enhanced GABAergic signaling during adolescence.
青春期是主要神经心理障碍出现的高度脆弱时期，其特征是认知控制能力下降、冒险行为增加和对新奇事物的追求增加。前额叶皮层（PFC）参与对冲动和冒险行为的认知控制。尽管已知PFC比其他皮层区域成熟得晚，但关于PFC从青春期到成年期的功能变化，尤其是与其他主要皮层区域相比的功能变化，目前所知甚少。本研究旨在了解与非PFC介导的认知功能相比，PFC介导的认知功能的发展情况。为实现这一目标，我们在青春期和成年小鼠中进行了认知行为任务，随后研究了两个不同皮层区域的突触可塑性。我们的结果表明，与成年小鼠相比，青春期小鼠在依赖PFC的认知任务中表现受损，而它们在非PFC依赖任务中的表现与成年小鼠相似。此外，青春期小鼠在PFC的上层突触中表现出长时程增强（LTP）降低，但在桶状皮层中未出现这种情况。阻断GABA受体功能可显著增强青春期和成年PFC中的LTP。在青春期和成年小鼠之间，未观察到PFC锥体神经元的内在兴奋性有变化。最后，仅在成年PFC中发现N-甲基-D-天冬氨酸受体的NR2A亚基表达增加，这一变化可能是LTP出现的基础。总之，我们的结果表明青春期存在特定于PFC的生理和行为变化，这可能是青少年认知控制能力下降的基础。新发现与值得注意之处 本研究报告称，青春期小鼠在依赖前额叶皮层的认知功能方面表现受损，但在依赖其他皮层区域的认知功能方面未受损。目前的结果表明，前额叶皮层上层突触可塑性降低是这种认知功能减弱的细胞相关因素。这种突触可塑性降低是由于N-甲基-D-天冬氨酸受体表达减少，而不是由于青春期内在兴奋性降低或GABA能信号增强。
