Scholarlink

<p>Synaptic dysfunction and resulting imbalance of excitatory vs. inhibitory transmission are fundamental aspects of autism spectrum disorders (ASD). Here we addressed the role of inhibitory synapse disturbances in ASD employing mice with a conditional ablation in GABAergic forebrain interneurons of the presynaptic active zone scaffolding protein Bassoon (Bsn), a key factor in synaptic development, activity and maintenance. The conditional <i>Bsn</i> gene knockout resulted in a reduction of synaptic vesicles and reduced synaptic efficacy of affected inhibitory synapses as well as diminished GABAergic inhibition of hippocampal pyramidal neurons. <i>Bsn</i> mutants further displayed a reconfiguration of the hippocampal synaptic network in vivo, as seen in subfield-specific changes of inhibitory synaptic markers and reduced parvalbumin interneuron labeling, culminating in disturbance of hippocampal network activity patterns and profound mitochondrial and metabolic dysregulation. Importantly, the mutant mice developed behavioral abnormalities reminiscent of ASD including widespread social behavioral deficits and novelty-induced hyperarousal with altered motor behavior, increased anxiety and epileptiform activity. <i>Bsn</i> conditional knockout mice thus provide strong evidence for a causal involvement of GABAergic synapses in the emergence of ASD-related behavioral and physiological phenotypes.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Autism-like behavior induced by conditional ablation of the Bassoon gene in GABAergic interneurons

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月29日

查看全文
  • Anil Annamneedi,
  • Carolina Montenegro-Venegas,
  • Gürsel Çalışkan,
  • Endre Levente Marosi,
  • Armand Blondiaux,
  • Nikhil Tiwari,
  • Misbah Razzaq,
  • Judith C. Kreutzmann,
  • Lucie P. Pellissier,
  • Anna Fejtova,
  • Sanja Mikulovic,
  • Markus Fendt,
  • Eckart D. Gundelfinger,
  • Oliver Stork

摘要

Synaptic dysfunction and resulting imbalance of excitatory vs. inhibitory transmission are fundamental aspects of autism spectrum disorders (ASD). Here we addressed the role of inhibitory synapse disturbances in ASD employing mice with a conditional ablation in GABAergic forebrain interneurons of the presynaptic active zone scaffolding protein Bassoon (Bsn), a key factor in synaptic development, activity and maintenance. The conditional Bsn gene knockout resulted in a reduction of synaptic vesicles and reduced synaptic efficacy of affected inhibitory synapses as well as diminished GABAergic inhibition of hippocampal pyramidal neurons. Bsn mutants further displayed a reconfiguration of the hippocampal synaptic network in vivo, as seen in subfield-specific changes of inhibitory synaptic markers and reduced parvalbumin interneuron labeling, culminating in disturbance of hippocampal network activity patterns and profound mitochondrial and metabolic dysregulation. Importantly, the mutant mice developed behavioral abnormalities reminiscent of ASD including widespread social behavioral deficits and novelty-induced hyperarousal with altered motor behavior, increased anxiety and epileptiform activity. Bsn conditional knockout mice thus provide strong evidence for a causal involvement of GABAergic synapses in the emergence of ASD-related behavioral and physiological phenotypes.