Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3Δex1-6) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.

中文翻译：

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有缺陷的突触传递导致幼年神经元蜡样脂褐质沉积症小鼠模型的疾病迹象

由 CLN3 基因突变引起的幼年神经元蜡样脂褐质沉积症（JNCL 或 Batten 病）是儿童时期最普遍的遗传性神经退行性疾病，导致广泛的中枢神经系统功能障碍和过早死亡。CLN3 突变对疾病进展、神经元传递和中枢神经网络功能障碍的影响知之甚少。我们使用了 Cln3 基因敲除 (Cln3Δex1-6) 小鼠，发现焦虑相关行为增加，厌恶学习受损，运动功能明显受影响，包括协调障碍。膜片钳和松散膜片记录显示杏仁核、海马和小脑网络中的抑制性和兴奋性突触传递受到严重影响。CLN3 蛋白功能障碍可能导致突触前释放特性的变化。此外，中央网络中钙结合蛋白、神经肽 Y、小清蛋白和 GAD65 阳性中间神经元的丢失共同支持了 GABA 能中间神经元的退化可能是脊髓上 GABA 能去抑制的原因的假设。