The 22q11.2 deletion has been identified as a risk factor for multiple neurodevelopmental disorders. Behavioral and cognitive impairments are common among carriers of the 22q11.2 deletion. Parvalbumin expressing (PV⁺) interneurons provide perisomatic inhibition of excitatory neuronal circuits through GABA_A receptors, and a deficit of PV⁺ inhibitory circuits may underlie a multitude of the behavioral and functional deficits in the 22q11.2 deletion syndrome. We investigated putative deficits of PV⁺ inhibitory circuits and the associated molecular, morphological, and functional alterations in the prefrontal cortex (PFC) of the Df(h22q11)/+ mouse model of the 22q11.2 hemizygous deletion. We detected a significant decrease in the number of PV⁺ interneurons in layers II/III of PFC in Df(h22q11)/+ mice together with a reduction in the mRNA and protein levels of GABA_A (α3), a PV⁺ putative postsynaptic receptor subunit. Pyramidal neurons from the same layers further experienced morphological reorganizations of spines and dendrites. Accordingly, a decrease in the levels of the postsynaptic density protein 95 (PSD95) and a higher neuronal activity in response to the GABA_A antagonist bicuculline were measured in these layers in PFC of Df(h22q11)/+ mice compared with their wild-type littermates. Our study shows that a hemizygotic deletion of the 22q11.2 locus leads to deficit in the GABAergic control of network activity and involves molecular and morphological changes in both the inhibitory and excitatory synapses of parvalbumin interneurons and pyramidal neurons specifically in layers II/III PFC.

22q11.2缺失已被确定为多种神经发育障碍的危险因素。行为和认知障碍在22q11.2缺失携带者中很常见。表达小白蛋白（PV ⁺）的中间神经元通过GABA _A受体提供兴奋性神经回路的过时抑制作用，PV ⁺抑制回路的缺陷可能是22q11.2缺失综合征中许多行为和功能缺陷的基础。我们调查了PV ^+的假定缺陷抑制电路和相关的分子，形态和功能的变化，在22q11.2半合缺失的Df（h22q11）/ +小鼠模型的前额叶皮层（PFC）中。我们检测到Df（h22q11）/ +小鼠的PFC的II / III层中PV ⁺中间神经元的数量显着减少，同时PV ⁺突触后受体GABA _A（α3）的mRNA和蛋白水平也降低了亚基。来自相同层的金字塔形神经元进一步经历了棘突和树突的形态重组。因此，响应GABA _A的突触后密度蛋白95（PSD95）的水平下降和神经元活性较高_。与野生型同窝仔相比，在Df（h22q11）/ +小鼠的PFC的这些层中测量了拮抗双小分子。我们的研究表明，22q11.2位点的半合子缺失导致网络活动的GABA能控制缺乏，并且涉及小白蛋白中间神经元和锥体神经元的抑制性和兴奋性突触的分子和形态变化，特别是在II / III PFC层。