Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible

被引：94
作者：
Goel, Anubhuti [1 ]
Cantu, Daniel A. [1 ]
Guilfoyle, Janna [2 ]
Chaudhari, Gunvant R. [1 ]
Newadkar, Aditi [1 ]
Todisco, Barbara [1 ]
de Alba, Diego [1 ]
Kourdougli, Nazim [1 ]
Schmitt, Lauren M. [2 ]
Pedapati, Ernest [2 ,3 ]
Erickson, Craig A. [2 ]
Portera-Cailliau, Carlos [1 ,4 ]
机构：
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[2] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45221 USA
[3] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Dept Neurol, Cincinnati, OH USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
来源：
NATURE NEUROSCIENCE | 2018年 / 21卷 / 10期
关键词：
EXPRESSING INTERNEURONS; INHIBITORY NEURONS; EVOKED POTENTIALS; SELECTIVITY; RESPONSES; DECISION; TARGET; AUTISM; CORTEX;
D O I：
10.1038/s41593-018-0231-0
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom- to-circuit approach in the Fmr1-knockout (Fmr1(-/-)) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1(-/-)mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1(-/-)mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1(-/-)mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome.
引用
收藏
页码：1404 / +
页数：11
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