Hyperexcitability in the Olfactory Bulb and Impaired Fine Odor Discrimination in the Fmr1 KO Mouse Model of Fragile X Syndrome

被引:0
作者
Kuruppath, Praveen [1 ]
Xue, Lin [1 ]
Pouille, Frederic [1 ]
Jones, Shelly T. [1 ,2 ]
Schoppa, Nathan E. [1 ]
机构
[1] Univ Colorado, Dept Physiol & Biophys, Anschutz Med Campus, Aurora, CO 80045 USA
[2] Univ Colorado, Neurosci Grad Program, Anschutz Med Campus, Aurora, CO 80045 USA
基金
美国国家卫生研究院;
关键词
autism spectrum disorders; fragile X syndrome; inhibition; mitral cell; odor discrimination; olfactory; MITRAL CELLS; NEURONAL HYPEREXCITABILITY; RESPONSES; SYNCHRONIZATION; OSCILLATIONS; PERCEPTION; ABNORMALITIES; DYSFUNCTION; INHIBITION; AMYGDALA;
D O I
10.1523/JNEUROSCI.0584-23.2023
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Fragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders (ASDs) in humans. FXS is caused by loss of expression of the fragile X mental retardation protein (FMRP), an mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. Sensory processing deficits have been a major focus of studies of FXS in both humans and rodent models of FXS, but olfactory deficits remain poorly understood. Here, we conducted experiments in wild-type (WT) and Fmr1 knock-out (KO; Fmr1(-/y)) mice (males) that lack expression of the gene encoding FMRP to assess olfactory circuit and behavioral abnormalities. In patch-clamp recordings conducted in slices of the olfactory bulb, output mitral cells (MCs) in Fmr1 KO mice displayed greatly enhanced excitation under baseline conditions, as evidenced by a much higher rate of occurrence of spontaneous network-level events known as long-lasting depolarizations (LLDs). The higher probability of spontaneous LLDs (sLLDs), which appeared to be because of a decrease in GABAergic synaptic inhibition in glomeruli leading to more feedforward excitation, caused a reduction in the reliability of stimulation-evoked responses in MCs. In addition, in a go/no-go operant discrimination paradigm, we found that Fmr1 KO mice displayed impaired discrimination of odors in difficult tasks that involved odor mixtures but not altered discrimination of monomolecular odors. We suggest that the Fmr1 KO-induced reduction in MC response reliability is one plausible mechanism for the impaired fine odor discrimination.
引用
收藏
页码:8243 / 8258
页数:16
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