Dataset Information

Atypical Response Properties of the Auditory Cortex of Awake MECP2-Overexpressing Mice.

ABSTRACT: Methyl-CpG binding protein 2 (MECP2) is a gene associated with DNA methylation and has been found to be important for maintaining brain function. In humans, overexpression of MECP2 can cause a severe developmental disorder known as MECP2 duplication syndrome. However, it is still unclear whether MECP2 overexpression also causes auditory abnormalities, which are common in people with autism. MECP2-TG is a mouse model of MECP2 duplication syndrome and has been widely used for research on social difficulty and other autism-like disorders. In this study, we used a combination of multiple electrophysiological techniques to document the response properties of the auditory cortex of awake MECP2-TG mice. Our results showed that while the auditory brainstem responses are similar, cortical activity patterns including local field potentials (LFPs), multiunit activity (MUA), and single-neuron responses differ between MECP2-TG and wild-type (WT) mice. At the single-neuron level, the spike waveform of fast-spiking (FS) neurons from MECP2-TG mice is different from that of WT mice, as reflected by reduced peak/trough ratios in the transgenic mice. Both regular-spiking (RS) and FS neurons exhibited atypical response properties in MECP2-TG mice compared with WT mice, such as prolonged latency and an elevated intensity threshold; furthermore, regarding the response strength to different stimuli, MECP2-TG mice exhibited stronger responses to noise than to pure tone, while this pattern was not observed in WT mice. Our findings suggest that MECP2 overexpression can cause the auditory cortex to have atypical response properties, an implication that could be helpful for further understanding the nature of auditory deficits in autism.

SUBMITTER: Zhou C

PROVIDER: S-EPMC6515258 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Atypical Response Properties of the Auditory Cortex of Awake MECP2-Overexpressing Mice.

Zhou Chang C Yan Sumei S Qian Shaowen S Wang Zhaoqun Z Shi Zhiyue Z Xiong Ying Y Zhou Yi Y

Frontiers in neuroscience 20190507

Methyl-CpG binding protein 2 (MECP2) is a gene associated with DNA methylation and has been found to be important for maintaining brain function. In humans, overexpression of MECP2 can cause a severe developmental disorder known as MECP2 duplication syndrome. However, it is still unclear whether MECP2 overexpression also causes auditory abnormalities, which are common in people with autism. MECP2-TG is a mouse model of MECP2 duplication syndrome and has been widely used for research on social di ...[more]

PMID: 31133783

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Project description:Songbirds learn to sing much as humans learn to speak. In zebra finches, one of the premier songbird models, males learn to sing for later courtship through a multistep learning process during the developmental period. They first listen to and memorize the song of a tutor (normally their father) during the sensory learning period. Then, in the subsequent sensory-motor learning phase (with large overlap), they match their vocalizations to the memorized tutor song via auditory feedback and develop their own unique songs, which they maintain throughout their lives. Previous studies have suggested that memories of tutor songs are shaped in the caudomedial nidopallium (NCM) of the brain, which is analogous to the mammalian higher auditory cortex. Isolation during development, which extends the sensory learning period in males, alters song preference in adult females, and NCM inactivation decreases song preference. However, the development of neurophysiological properties of neurons in this area and the effect of isolation on these neurons have not yet been explained. Here, we performed whole-cell patch-clamp recording on NCM neurons from juvenile zebra finches during the sensory learning period, 20, 40, or 60 days post-hatching (DPH) and examined their neurophysiological properties. In contrast to previous reports in adult NCM neurons, the majority of NCM neurons of juvenile zebra finches showed spontaneous firing with or without burst firing patterns, and the percentage of neurons that fired increased in the middle of the sensory learning period (40 DPH) and then decreased at the end (60 DPH) in both males and females. We further found that auditory isolation from tutor songs alters developmental changes in the proportions of firing neurons both in males and females, and also changes those of burst neurons differently between males that sing and females that do not. Taken together, these findings suggest that NCM neurons develop their neurophysiological properties depending on auditory experiences during the sensory song learning period, which underlies memory formation for song learning in males and song discrimination in females.

Dataset Information

Atypical Response Properties of the Auditory Cortex of Awake MECP2-Overexpressing Mice.

Publications

Atypical Response Properties of the Auditory Cortex of Awake MECP2-Overexpressing Mice.

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