共济失调-扩血管症突变基因（ATM）是一种丝氨酸/苏氨酸蛋白激酶，其主要作用是在DNA双链断裂（DSB）时组织DNA修复过程。Atm基因的突变导致共济失调-扩血管症（AT），这是一种由小脑萎缩或功能障碍引起的隐性疾病，同时伴有免疫改变、基因组不稳定性和癌症易感性。AT患者表现出变化多样的表型，从神经功能异常和认知障碍到近期描述的与ATM经典功能不相关的神经精神症状。事实上，有证据表明认知能力依赖于DSB机制的正常功能，ATM缺陷小鼠中中枢神经元突触的特定结构和功能变化揭示了ATM在突触中的意外作用。因此，在本综述中，我们回顾了DNA损伤应答，并重点关注ATM在神经生理学和病理学中的作用，并讨论了AT小鼠模型中海马和皮层突触的结构和功能变化的最新发现。总之，深入了解ATM在神经元中的依赖机制不仅有助于更好地理解AT的神经表型，还有助于更好地理解与ATM功能障碍相关的神经发育和退行性疾病的病理机制。

Ataxia-Telangiectasia Mutated (ATM) is a serine/threonine protein kinase principally known to orchestrate DNA repair processes upon DNA double-strand breaks (DSBs). Mutations in the Atm gene lead to Ataxia-Telangiectasia (AT), a recessive disorder characterized by ataxic movements consequent to cerebellar atrophy or dysfunction, along with immune alterations, genomic instability, and predisposition to cancer. AT patients show variable phenotypes ranging from neurologic abnormalities and cognitive impairments to more recently described neuropsychiatric features pointing to symptoms hardly ascribable to the canonical functions of ATM in DNA damage response (DDR). Indeed, evidence suggests that cognitive abilities rely on the proper functioning of DSB machinery and specific synaptic changes in central neurons of ATM-deficient mice unveiled unexpected roles of ATM at the synapse. Thus, in the present review, upon a brief recall of DNA damage responses, we focus our attention on the role of ATM in neuronal physiology and pathology and we discuss recent findings showing structural and functional changes in hippocampal and cortical synapses of AT mouse models. Collectively, a deeper knowledge of ATM-dependent mechanisms in neurons is necessary not only for a better comprehension of AT neurological phenotypes, but also for a higher understanding of the pathological mechanisms in neurodevelopmental and degenerative disorders involving ATM dysfunctions.