School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK.
Neuroscience@Nottingham, University of Nottingham, Nottingham NG7 2RD, UK.
Cereb Cortex. 2017 Sep 1;27(9):4447-4462. doi: 10.1093/cercor/bhw247.
Subconvulsive hippocampal neural disinhibition, that is reduced GABAergic inhibition, has been implicated in neuropsychiatric disorders characterized by attentional and memory deficits, including schizophrenia and age-related cognitive decline. Considering that neural disinhibition may disrupt both intra-hippocampal processing and processing in hippocampal projection sites, we hypothesized that hippocampal disinhibition disrupts hippocampus-dependent memory performance and, based on strong hippocampo-prefrontal connectivity, also prefrontal-dependent attention. In support of this hypothesis, we report that acute hippocampal disinhibition by microinfusion of the GABA-A receptor antagonist picrotoxin in rats impaired hippocampus-dependent everyday-type rapid place learning performance on the watermaze delayed-matching-to-place test and prefrontal-dependent attentional performance on the 5-choice-serial-reaction-time test, which does not normally require the hippocampus. For comparison, we also examined psychosis-related sensorimotor effects, using startle/prepulse inhibition (PPI) and locomotor testing. Hippocampal picrotoxin moderately increased locomotion and slightly reduced startle reactivity, without affecting PPI. In vivo electrophysiological recordings in the vicinity of the infusion site showed that picrotoxin mainly enhanced burst firing of hippocampal neurons. In conclusion, hippocampal neural disinhibition disrupts hippocampus-dependent memory performance and also manifests through deficits in not normally hippocampus-dependent attentional performance. These behavioral deficits may reflect a disrupted control of burst firing, which may disrupt hippocampal processing and cause aberrant drive to hippocampal projection sites.
亚惊厥海马神经去抑制，即 GABA 能抑制减少，与以注意力和记忆缺陷为特征的神经精神疾病有关，包括精神分裂症和与年龄相关的认知衰退。考虑到神经去抑制可能破坏海马内处理和海马投射部位的处理，我们假设海马去抑制破坏海马依赖性记忆表现，并且基于强大的海马-前额叶连接，还破坏前额叶依赖性注意力。支持这一假设，我们报告说，在大鼠中通过微注射 GABA-A 受体拮抗剂荷包牡丹碱急性海马去抑制，损害了在水迷宫延迟匹配位置测试中的海马依赖性日常快速位置学习表现，以及在不通常需要海马的 5 选择连续反应时间测试中的前额叶依赖性注意力表现。作为比较，我们还使用惊跳/预脉冲抑制 (PPI) 和运动测试检查了与精神病相关的感觉运动效应。海马荷包牡丹碱中度增加了运动，轻微降低了惊跳反应，而不影响 PPI。在输注部位附近的体内电生理记录表明，荷包牡丹碱主要增强了海马神经元的爆发放电。总之，海马神经去抑制破坏了海马依赖性记忆表现，并且还表现为通常不依赖海马的注意力表现缺陷。这些行为缺陷可能反映了爆发放电控制的破坏，这可能破坏海马处理并导致对海马投射部位的异常驱动。
