Department of Psychology, Temple University, Philadelphia, Pennsylvania, USA.
Neuroscience Program, Temple University, Philadelphia, Pennsylvania, USA.
Addict Biol. 2022 Jan;27(1):e13077. doi: 10.1111/adb.13077. Epub 2021 Jul 18.
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 behaviour. 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.
儿童期和青少年期的逆境暴露会增加个体易患物质使用障碍的风险。尽管人们已经了解到这种脆弱性，但其中的机制仍知之甚少。伏隔核（NAc）的兴奋性传入纤维介导了对压力和奖励刺激的反应。了解青少年社交隔离如何改变这些传入纤维，可以为药物使用前后的靶向干预措施提供信息。在这里，我们使用社交隔离饲养作为早期生活逆境的模型，我们之前已经证明它会增加对可卡因成瘾样行为的易感性。本研究检查了社交隔离饲养对雄性和雌性小鼠 NAc 中中型多棘神经元的突触前谷氨酸能传递的影响。我们发现，社交隔离饲养通过降低成对脉冲比和谷氨酸可释放池的大小来改变 NAc 中的突触前可塑性。光遗传学激活腹侧海马到 NAc 的谷氨酸能传入足以再现电刺激所有 NAc 传入纤维后观察到的成对脉冲比和可释放池大小的降低。此外，在电刺激期间光遗传学抑制腹侧海马传入可以消除早期生活逆境对成对脉冲比或可释放池大小的影响。总之，我们证明了社交隔离饲养会导致腹侧海马投射驱动的谷氨酸传递发生变化。这些数据表明，靶向腹侧海马到伏隔核的回路可能提供一种逆转应激诱导可塑性的方法。
