Adolescent social isolation induced alterations in nucleus accumbens glutamate signalling.
Adolescent social isolation induced alterations in nucleus accumbens glutamate signalling.
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DOI：
10.1111/adb.13077
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Briand, Lisa A.
中科院分区：
文献类型：
--
作者：
Deutschmann, Andre U.;Kirkland, Julia M.;Briand, Lisa A.
关键词：
在幼儿期和青春期暴露于逆境会增加个人发展药物使用障碍的脆弱性。尽管对这种脆弱性有所了解，但对其内在机制仍然知之甚少。兴奋性传入神经核（NAc）介导的反应，压力和奖励的刺激。了解青少年的社会隔离如何改变这些传入可以告知吸毒前后有针对性的干预措施的发展。在这里，我们使用社会隔离养育作为早期生活逆境的模型，我们以前已经证明了对可卡因成瘾样行为的脆弱性。本研究探讨了社会隔离饲养对雄性和雌性小鼠NAc中棘神经元突触前突触能传递的影响。我们发现，社会隔离饲养改变突触前可塑性的NAC通过降低成对脉冲比和大小的谷氨酸容易释放池。光遗传学激活腹侧海马到NAc的神经元能输入足以概括所有NAc传入的电刺激后看到的配对脉冲比和容易释放的池大小的减少。此外，在电刺激期间光遗传学抑制腹侧海马传入消除了早期生活逆境对成对脉冲比或容易释放的池大小的影响。总之，我们表明，社会隔离饲养导致谷氨酸传输的腹侧海马体的预测驱动的改变。这些数据表明，针对腹侧海马回到丘脑核的回路可以提供一种逆转应激诱导的可塑性的方法。
Exposure to adversity during early childhood and adolescence increases an individual’s vulnerability to developing substance use disorder. Despite the knowledge of this vulnerability, the mechanisms underlying it are still poorly understood. Excitatory afferents to the nucleus accumbens (NAc) mediate responses to both stressful and rewarding stimuli. Understanding how adolescent social isolation alters these afferents could inform the development of targeted interventions both before and after drug use. Here, we used social isolation rearing as a model of early life adversity which we have previously demonstrated increases vulnerability to cocaine addiction-like behavior. The current study examined the effect of social isolation rearing on presynaptic glutamatergic transmission in NAc medium spiny neurons in both male and female mice. We show that social isolation rearing alters presynaptic plasticity in the NAc by decreasing the paired-pulse ratio and the size of the readily releasable pool of glutamate. Optogenetically activating the glutamatergic input from the ventral hippocampus to the NAc is sufficient to recapitulate the decreases in paired-pulse ratio and readily releasable pool size seen following electrical stimulation of all NAc afferents. Further, optogenetically inhibiting the ventral hippocampal afferent during electrical stimulation eliminates the effect of early life adversity on the paired-pulse ratio or readily releasable pool size. In summary, we demonstrate that social isolation rearing leads to alterations in glutamate transmission driven by projections from the ventral hippocampus. These data suggest that targeting the circuit from the ventral hippocampus to the nucleus accumbens could provide a means to reverse stress-induced plasticity.
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影响因子：
3.3
作者：
Brancato A;Bregman D;Ahn HF;Pfau ML;Menard C;Cannizzaro C;Russo SJ;Hodes GE
通讯作者：
Hodes GE
DOI：
10.1073/pnas.0908563106
发表时间：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Briand LA
DOI：
10.1073/pnas.1917423117
发表时间：
2020-04-07
影响因子：
11.1
作者：
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通讯作者：
Grassi, Claudio