It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress
It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress
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DOI：
10.1523/jneurosci.1029-20.2020
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发表时间：
2020-10-21
影响因子：
5.3
通讯作者：
Walker, Claire-Dominique
中科院分区：
文献类型：
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作者：
Guadagno, Angela;Verlezza, Silvanna;Walker, Claire-Dominique
早期生活压力（ELS）与精神障碍的易感性增加有关。基底外侧杏仁核（BLA）在恐惧条件反射中起关键作用，对ELS极其敏感。利用自然啮齿类动物ELS模型，即出生后1-10天的有限床上模式（LB），我们之前记录了LB雄性而非雌性断奶前大鼠幼崽表现出增加的BLA神经元脊柱密度，并与增强的诱发突触反应和改变的BLA功能连接相平行。由于ELS效应通常是两性二态的，杏仁核过程表现出半球不对称，我们在体外研究了出生后22-28天正常卧位或LB母亲的雄性和雌性后代左杏仁核和右杏仁核BLA神经元突触可塑性和神经元兴奋性的变化。我们报告说，LB条件只增强了雄性右侧脑区突触的可塑性，而不是左侧脑区。LB雄鼠也表现出神经周围净密度增加，特别是在小白蛋白（PV）细胞周围，并且仅在右侧BLA中，PV中间神经元的恐惧诱导活性受损。与正常床褥雌性相比，LB雌性右侧BLA神经元发射的动作电位表现出最大去极化速率减慢和振幅下降，同时右侧BLA中NMDAR GluN1亚基表达减少。在LB男性中，右侧BLA中GluA2表达的减少可能导致LTP的增加。这些结果表明，LB对左、右BLA突触可塑性和PV/神经元周围网络发育的调控存在差异。此外，我们的研究表明，ELS暴露对BLA突触功能的影响是两性二态的，可能涉及不同的机制。
Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons in vitro in the left and right amygdala of postnatal days 22-28 male and female offspring from normal bedding or LB mothers. We report that LB conditions enhanced synaptic plasticity in the right, but not the left BLA of males exclusively. LB males also showed increased perineuronal net density, particularly around parvalbumin (PV) cells, and impaired fear-induced activity of PV interneurons only in the right BLA. Action potentials fired from right BLA neurons of LB females displayed slower maximal depolarization rates and decreased amplitudes compared with normal bedding females, concomitant with reduced NMDAR GluN1 subunit expression in the right BLA. In LB males, reduced GluA2 expression in the right BLA might contribute to the enhanced LTP. These findings suggest that LB differentially programs synaptic plasticity and PV/perineuronal net development in the left and right BLA. Furthermore, our study demonstrates that the effects of ELS exposure on BLA synaptic function are sexually dimorphic and possibly recruiting different mechanisms.