14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway.
14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway.
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DOI：
10.3389/fnmol.2022.817227
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发表时间：
2022
影响因子：
4.8
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Zhang J;Navarrete M;Wu Y;Zhou Y
虽然人类和动物的研究都表明，海马体多动与精神病有关，但它是否会导致多巴胺能状态和潜在的神经回路仍然难以捉摸。先前的研究证实，背侧海马区CA1(DCA1)中14-3-3蛋白的区域特异性抑制会诱导小鼠的精神分裂症样行为，包括新奇诱导的运动多动。在这项研究中，我们发现dCA1的14-3-3功能障碍会过度激活腹侧被盖区(VTA)的多巴胺能神经元，这种过度激活是诱发小鼠精神运动行为所必需的。我们证明，在精神运动行为中，海马对VTA的这种失调依赖于外侧隔(LS)的过度激活，因为抑制LS可以减弱多巴胺能神经元的过度激活和dCA1中14-3-3抑制所引起的精神运动行为。此外，14-3-3抑制诱导的dCA1-LS-VTA通路内神经元的激活和精神运动行为可以通过LS投射的dCA1神经元的直接化学激活而复制。综上所述，这些结果表明，dCA1的14-3-3功能障碍导致了海马区的过度激活，从而通过dCA1-LS-VTA通路导致精神运动行为。
While hippocampal hyperactivity is implicated in psychosis by both human and animal studies, whether it induces a hyperdopaminergic state and the underlying neural circuitry remains elusive. Previous studies established that region-specific inhibition of 14-3-3 proteins in the dorsal hippocampus CA1 (dCA1) induces schizophrenia-like behaviors in mice, including a novelty-induced locomotor hyperactivity. In this study, we showed that 14-3-3 dysfunction in the dCA1 over-activates ventral tegmental area (VTA) dopaminergic neurons, and such over-activation is necessary for eliciting psychomotor behavior in mice. We demonstrated that such hippocampal dysregulation of the VTA during psychomotor behavior is dependent on an over-activation of the lateral septum (LS), given that inhibition of the LS attenuates over-activation of dopaminergic neurons and psychomotor behavior induced by 14-3-3 inhibition in the dCA1. Moreover, 14-3-3 inhibition-induced neuronal activations within the dCA1-LS-VTA pathway and psychomotor behavior can be reproduced by direct chemogenetic activation of LS-projecting dCA1 neurons. Collectively, these results suggest that 14-3-3 dysfunction in the dCA1 results in hippocampal hyperactivation which leads to psychomotor behavior via a dCA1-LS-VTA pathway.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
16.2
作者：
Broadie, K;Rushton, E;Davis, RL
通讯作者：
Davis, RL
影响因子：
5.4
作者：
Graham, Kourtney;Zhang, Jiajing;Zhou, Yi
通讯作者：
Zhou, Yi
影响因子：
3.5
作者：
Ikeda, Masashi;Hikita, Takao;Iwata, Nakao
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Iwata, Nakao
影响因子：
5.6
作者：
Aitta-aho, Teemu;Maksimovic, Milica;Korpi, Esa R.
通讯作者：
Korpi, Esa R.