Postnatal Phencyclidine-Induced Deficits in Decision Making Are Ameliorated by Optogenetic Inhibition of Ventromedial Orbitofrontal Cortical Glutamate Neurons.
Postnatal Phencyclidine-Induced Deficits in Decision Making Are Ameliorated by Optogenetic Inhibition of Ventromedial Orbitofrontal Cortical Glutamate Neurons.
复制标题
DOI：
10.1016/j.bpsgos.2023.08.002
复制
发表时间：
2024-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
The orbitofrontal cortex (OFC) is essential for decision making, and functional disruptions within the OFC are evident in schizophrenia. Postnatal phencyclidine (PCP) administration in rats is a neurodevelopmental manipulation that induces schizophrenia-relevant cognitive impairments. We aimed to determine whether manipulating OFC glutamate cell activity could ameliorate postnatal PCP-induced deficits in decision making. Male and female Wistar rats (n = 110) were administered saline or PCP on postnatal days 7, 9, and 11. In adulthood, we expressed YFP (yellow fluorescent protein) (control), ChR2 (channelrhodopsin-2) (activation), or eNpHR 3.0 (enhanced halorhodopsin) (inhibition) in glutamate neurons within the ventromedial OFC (vmOFC). Rats were tested on the probabilistic reversal learning task once daily for 20 days while we manipulated the activity of vmOFC glutamate cells. Behavioral performance was analyzed using a Q-learning computational model of reinforcement learning. Compared with saline-treated rats expressing YFP, PCP-treated rats expressing YFP completed fewer reversals, made fewer win-stay responses, and had lower learning rates. We induced similar performance impairments in saline-treated rats by activating vmOFC glutamate cells (ChR2). Strikingly, PCP-induced performance deficits were ameliorated when the activity of vmOFC glutamate cells was inhibited (halorhodopsin). Postnatal PCP-induced deficits in decision making are associated with hyperactivity of vmOFC glutamate cells. Thus, normalizing vmOFC activity may represent a potential therapeutic target for decision-making deficits in patients with schizophrenia.
登录
查看更多内容
通过发育绘制精神分裂症突触可塑性受损的后果：不同临床特征的综合模型。
影响因子：
19.9
作者：
Forsyth JK;Lewis DA
通讯作者：
Lewis DA
影响因子：
1.9
作者：
Cole S;Stone AD;Petrovich GD
通讯作者：
Petrovich GD
影响因子：
1.7
作者：
Green, M F;Kern, R S;Kee, K
通讯作者：
Kee, K
影响因子：
10.6
作者：
Bissonette, Gregory B.;Schoenbaum, Geoffrey;Powell, Elizabeth M.
通讯作者：
Powell, Elizabeth M.
影响因子：
4.7
作者：
Golitabari, Nastaran;Mohammadian, Forouzan;Amani, Mohammad
通讯作者：
Amani, Mohammad