Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields
Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields
复制标题
DOI：
10.1523/jneurosci.0630-17.2017
复制
发表时间：
2017-12-06
影响因子：
5.3
通讯作者：
Fenton, Andre A.
中科院分区：
文献类型：
--
作者：
Kao, Hsin-Yi;Dvorak, Dino;Fenton, Andre A.
我们使用拟精神病药物苯环利定（PCP）来研究海马位置细胞系统中认知行为、协调神经网络功能和信息处理之间的关系。我们报告在大鼠中，PCP（5 mg/kg，i. p.）损害了大鼠的一种良好学习的、依赖于海马的位置回避行为，这种行为需要认知控制，即使将五氯苯酚直接注射到背侧海马中也是如此。PCP增加海马CA 1区60-100 Hz中频伽马振荡，这些增加与全身PCP给药引起的认知障碍相关。PCP使CA 1 LFP中的θ调制中频和慢伽马振荡不协调，使得中频伽马振荡变得比慢伽马振荡更有θ组织。CA 1位置细胞放电场在PCP下被保留，但药物使位置细胞之间放电的亚秒时间组织不协调。这种不协调导致一个熟悉的空间的位置细胞系综表示停止类似于前PCP表示，尽管保存的地方字段。这些发现指出，PCP引起的认知障碍是由神经失调引起的。五氯酚干扰放电的时间相对于亚秒的时间尺度的θ和γ振荡在LFP。由于这些振荡产生于局部抑制性突触活动，这些发现表明兴奋-抑制失调是PCP诱导的认知障碍的根源。
We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p.) impairs a well learned, hippocampus-dependent place avoidance behavior in rats that requires cognitive control even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium-freguency gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium-frequency and slow gamma oscillations in CA1 LFPs such that medium-frequency gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP, but the drug discoordinates the subsecond temporal organization of discharge among place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the subsecond timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitation-inhibition discoordination as the root of PCP-induced cognitive impairment.