Alterations in the balance between excitation and inhibition, especially in the brain’s critical developmental periods, are considered an integral part of the pathophysiology of autism. However, the precise mechanisms have not yet been established. SH3 and multiple Ankyrin repeat domains 3 (Shank3) deficient mice represent a well-established transgenic model of a neurodevelopmental disorder with autistic symptomatology. In this study, we characterize the consequences of Shank3 deficiency according to (1) expression of specific markers of different neuronal populations in pups and adult mice and (2) social behaviour and anxiety in adult mice. Our research found enhanced expression of serotonin transporter and choline acetyltransferase in the hippocampus and hypothalamus in Shank3-deficient pups. We demonstrated marked brain region differences in expression of excitatory glutamatergic markers in pups and adult Shank3 deficient mice. We also observed reduced expression of inhibitory GABAergic markers and GABA receptor subunits in several brain areas in both pups and adult Shank3 deficient mice. Further analysis of dopaminergic brain areas (nucleus accumbens, ventral tegmental area) revealed lower expression levels of GABAergic markers in adult Shank3 deficient mice. Adult Shank3⁻ deficient mice exhibited excessive repetitive behaviour, a higher level of anxiety, and lower locomotor activity. Our data support the theory of an imbalance between excitatory and inhibitory neurotransmission in conditions of abnormal SHANK3 protein. We therefore suggest that autism-like conditions are accompanied by reduced expression of GABAergic markers in the brain during early development as well as in the adult age, which could be associated with long-lasting behavioural abnormalities.

兴奋和抑制之间平衡的改变，特别是在大脑的关键发育时期，被认为是自闭症病理生理学的一个组成部分。然而，确切的机制尚未建立。SH3 和多个锚蛋白重复结构域 3 ( Shank3 ) 缺陷小鼠代表了具有自闭症症状的神经发育障碍的成熟转基因模型。在这项研究中，我们根据（1）幼崽和成年小鼠中不同神经元群体的特定标记物的表达以及（2）成年小鼠的社会行为和焦虑来描述Shank3缺陷的后果。我们的研究发现海马和下丘脑中血清素转运蛋白和胆碱乙酰转移酶的表达增强Shank3缺陷的幼崽。我们证明了幼鼠和成年Shank3缺陷小鼠的大脑区域兴奋性谷氨酸标记物的表达存在显着差异。我们还观察到幼鼠和成年Shank3缺陷小鼠的几个大脑区域中抑制性 GABA 能标记物和 GABA 受体亚基的表达减少。对多巴胺能大脑区域（伏核、腹侧被盖区）的进一步分析显示，成年Shank3缺陷小鼠中 GABA 能标记物的表达水平较低。成人小腿3 ^-缺陷小鼠表现出过度的重复行为、更高水平的焦虑和较低的运动活动。我们的数据支持异常 SHANK3 蛋白条件下兴奋性和抑制性神经传递之间不平衡的理论。因此，我们认为，在早期发育期间以及成年时期，类似自闭症的病症都伴随着大脑中 GABA 能标记物表达的减少，这可能与长期行为异常有关。