Frequency-dependent cerebellar circuits independently gate social vocalizations and movement.

IF 4.5 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
iScience Pub Date : 2026-09-30 eCollection Date: 2026-10-16 DOI:10.1016/j.isci.2026.117706
Cheryl Brandenburg, Snigdha Srivastava, Alejandro G Rey Hipolito, Tao Lin, Benjamin R Arenkiel, Roy V Sillitoe
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引用次数: 0

Abstract

Communication depends on precise coordination between motor execution and cognition. Here we reveal that the cerebellum exerts real-time control over social vocalizations in adult mice. Optogenetic activation of excitatory cerebellar output in the superior cerebellar peduncle suppressed ultrasonic vocalizations with frequency-dependent potency while inducing distinct motor phenotypes. Systematic functional mapping across cerebellar regions and cell types revealed that vocal suppression can occur in the absence of overt motor impairment, suggesting selective control of vocal output beyond gross movement disruption. We identified the periaqueductal gray (PAG), a conserved midbrain vocal control center, as a key downstream mediator of this effect. Deep brain stimulation of the PAG rescued vocal deficits in a model of cerebellar dysfunction without rescuing motor incoordination. These findings define a cerebellar-midbrain pathway that gates vocal behavior and demonstrate that targeted therapeutic neuromodulation can selectively restore communication-related output even in the presence of persistent cerebellar-driven motor deficits.

频率相关的小脑回路独立地控制社会发声和运动。
沟通依赖于运动执行和认知之间的精确协调。在这里,我们揭示了小脑对成年小鼠的社会发声施加实时控制。光遗传激活小脑上脚的兴奋性小脑输出抑制了频率依赖性的超声发声,同时诱导了不同的运动表型。跨越小脑区域和细胞类型的系统功能图谱显示,在没有明显运动障碍的情况下,声音抑制也会发生,这表明在大运动中断之外,有选择性地控制声音输出。我们确定了导水管周围灰质(PAG),一个保守的中脑声音控制中心,作为这种作用的关键下游介质。PAG脑深部刺激可挽救小脑功能障碍模型的声带缺陷,但不能挽救运动不协调。这些发现定义了一个控制发声行为的小脑-中脑通路,并证明了靶向治疗性神经调节可以选择性地恢复沟通相关的输出,即使在持续存在小脑驱动的运动缺陷的情况下。
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来源期刊
iScience
iScience Multidisciplinary-Multidisciplinary
CiteScore
7.20
自引率
1.70%
发文量
1972
审稿时长
6 weeks
期刊介绍: Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.
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