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Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior
eLife ( IF 6.4 ) Pub Date : 2020-09-21 , DOI: 10.7554/elife.56171
Sthitapranjya Pati 1 , Kamal Saba 2 , Sonali S Salvi 1 , Praachi Tiwari 1 , Pratik R Chaudhari 1 , Vijaya Verma 3 , Sourish Mukhopadhyay 1 , Darshana Kapri 1 , Shital Suryavanshi 1 , James P Clement 3 , Anant B Patel 2 , Vidita A Vaidya 1
Affiliation  

Early adversity is a risk factor for the development of adult psychopathology. Common across multiple rodent models of early adversity is increased signaling via forebrain Gq-coupled neurotransmitter receptors. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke persistent mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated chemogenetic activation of forebrain excitatory neurons during postnatal life (P2–14), but not in juvenile or adult windows, increased anxiety-, despair-, and schizophrenia-like behavior in adulthood. This was accompanied by an enhanced metabolic rate of cortical and hippocampal glutamatergic and GABAergic neurons. Furthermore, we observed reduced activity and plasticity-associated marker expression, and perturbed excitatory/inhibitory currents in the hippocampus. These results indicate that Gq-signaling-mediated activation of forebrain excitatory neurons during the critical postnatal window is sufficient to program altered mood-related behavior, as well as functional changes in forebrain glutamate and GABA systems, recapitulating aspects of the consequences of early adversity.

中文翻译:

前脑兴奋性神经元的慢性出生后化学遗传激活引起情绪行为的持续变化

早期逆境是成人精神病理学发展的危险因素。早期逆境的多个啮齿动物模型的共同点是通过前脑 Gq 耦合神经递质受体增加信号。我们讨论了出生后前脑兴奋性神经元中增强的 Gq 介导的信号传导是否会引起持续的情绪相关行为变化。兴奋性 hM3Dq DREADD 介导的出生后生活中前脑兴奋性神经元的化学遗传激活(P2-14),但不是在青少年或成人窗口中,成年后焦虑、绝望和精神分裂症样行为增加。这伴随着皮质和海马谷氨酸能和 GABA 能神经元的代谢率提高。此外,我们观察到活性和可塑性相关标记表达降低,和扰动海马体中的兴奋/抑制电流。这些结果表明,在关键的出生后窗口期间,Gq 信号介导的前脑兴奋性神经元激活足以编程改变的情绪相关行为,以及前脑谷氨酸和 GABA 系统的功能变化,概括早期逆境后果的各个方面。
更新日期:2020-09-21
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