Molecular Physiology of Hearing, Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, University of Tübingen, Tübingen, Germany.
Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
FASEB J. 2024 Jan 31;38(2):e23411. doi: 10.1096/fj.202301995R.
Autism spectrum disorder is discussed in the context of altered neural oscillations and imbalanced cortical excitation-inhibition of cortical origin. We studied here whether developmental changes in peripheral auditory processing, while preserving basic hearing function, lead to altered cortical oscillations. Local field potentials (LFPs) were recorded from auditory, visual, and prefrontal cortices and the hippocampus of Bdnf KO mice. These mice develop an autism-like behavioral phenotype through deletion of BDNF in Pax2+ interneuron precursors, affecting lower brainstem functions, but not frontal brain regions directly. Evoked LFP responses to behaviorally relevant auditory stimuli were weaker in the auditory cortex of Bdnf KOs, connected to maturation deficits of high-spontaneous rate auditory nerve fibers. This was correlated with enhanced spontaneous and induced LFP power, excitation-inhibition imbalance, and dendritic spine immaturity, mirroring autistic phenotypes. Thus, impairments in peripheral high-spontaneous rate fibers alter spike synchrony and subsequently cortical processing relevant for normal communication and behavior.
自闭症谱系障碍是在神经振荡改变和皮质起源的兴奋-抑制失衡的背景下讨论的。我们在这里研究了外周听觉处理的发育变化是否会导致皮质振荡改变，而基本的听觉功能保持不变。局部场电位 (LFPs) 记录于听觉、视觉和前额皮质以及 Bdnf KO 小鼠的海马体中。这些小鼠通过在 Pax2+中间神经元前体中删除 BDNF 而发展出类似自闭症的行为表型，影响脑干下部功能，但不直接影响额叶脑区。与高自发性听觉神经纤维的成熟缺陷相关，BDNF KO 小鼠的听觉皮层对行为相关听觉刺激的诱发电位 LFP 反应较弱。这与自发性和诱发性 LFP 功率增强、兴奋-抑制失衡和树突棘不成熟相关，反映了自闭症表型。因此，外周高自发性纤维的损伤改变了尖峰同步性，进而影响了正常交流和行为相关的皮质处理。
