Pubmed du 18/05/25
1. Chari T, Hernandez A, Couto J, Portera-Cailliau C. A reduced ability to discriminate social from non-social touch at the circuit level may underlie social avoidance in autism. Nat Commun. 2025; 16(1): 4600.
Social touch is critical for communication to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch. Here, we used Neuropixels probes to record neural responses to social vs. non-social interactions in somatosensory cortex, tail of striatum, and basolateral amygdala. We find that wild type mice show aversion to repeated presentations of an inanimate object but not of another mouse. Cortical neurons are modulated especially by touch context (social vs. object), while striatal neurons change their preference depending on whether mice could choose or not to interact. In contrast, Fmr1 knockout (KO) mice, a model of autism, find social and non-social interactions equally aversive, especially at close proximity, and their cortical/striatal neurons are less able to discriminate social valence. A linear model shows that the encoding of certain avoidance/aversive behaviors in cortical neuron activity differed between genotypes. Thus, a reduced capacity to represent social stimuli at the circuit level may underlie social avoidance in autism.
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2. Deane KE, Binder DK, Razak KA. Cortical layer-specific abnormalities in auditory responses in a mouse model of Fragile X Syndrome. Neurobiol Dis. 2025; 212: 106963.
Fragile X Syndrome (FXS) is a leading genetic cause of autism spectrum disorders (ASD)- associated behaviors, including sensory processing deficits. Sensory sensitivity and temporal processing deficits in the auditory domain will affect development of language and cognitive functions. The mouse model for FXS, Fmr1 KO, has shown remarkably similar auditory processing phenotypes to patients with FXS. In vitro cortical slice recordings show layer-specific differences in Fmr1 KO mouse local circuits, but it is unclear how these differences translate to changes in sensory processing. In this study, we used a depth multielectrode to record in vivo spikes and local field potentials across layers of the auditory cortex in Fmr1 KO and wildtype mice (WT), converting the latter to current source density (CSD) profiles for improved spatial resolution analysis. We observed reduced CSD sink amplitudes and inter-trial phase coherence, and an increase in trial-to-trial variability for temporally modulated stimuli in the KO mice. Results indicated a differential cortical layer pattern of activity in KO mice, with higher baseline gamma power in superficial and deep layers and higher resting delta and theta power in granular layers. Significantly elevated inter-trial variability was observed for CSD and spikes in KO mice. Auditory steady state responses to clicks or gaps at 40 Hz showed considerable trial-to-trial variability in a layer-specific manner in KO mice. Neural generators in the Fmr1 KO mouse auditory cortex failed to detect short gaps in noise, indicating severe temporal processing deficits. Altogether, this study indicates layer-specific cortical mechanisms of sensory hypersensitivity and temporal processing deficits in FXS.
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3. Dy-Hollins ME, Kapur K, Prohl AK, Sharma N, Yang E, Warfield SK, Waugh JL. Globally Reduced Brain Volume in Rett Syndrome. Pediatr Neurol. 2025; 168: 60-6.
BACKGROUND: To compare global and regional brain volumes between individuals with Rett syndrome (RTT) and two independent control groups (typically developing [TD], idiopathic developmental delay [DD]) using direct patient:control matching, higher-resolution magnetic resonance imaging (MRI) scans, and larger samples than were available in prior RTT studies. METHODS: Control cohorts were age and sex matched 1:1 with RTT. We utilized the PSTAPLE algorithm to conduct MRI-based anatomic segmentations and quantify global and regional volumetry. RESULTS: A total of 42 subjects (14 per group) were included with mean age 8.0 years ± 6.1 S.D. (range: 1.4-20.7 years). Global and regional brain volumes were compared between groups with analysis of covariance. Intracranial cavity volume was regressed as a variable of interest; the log of age at scan was regressed as a variable of no interest. Global and regional volumes were reduced in RTT (versus DD and TD). Total gray matter was reduced by 19% in RTT (versus TD and DD). Similar volumetric reductions were noted in occipital, parietal, and temporal cortices in RTT (versus TD and DD). Cerebellar white matter was reduced in RTT (3.4%; versus DD only). CONCLUSIONS: MRI findings in individuals with RTT demonstrated global reductions in brain volume with relatively uniform involvement of cortical and subcortical structures. Cerebellar white matter volume may be reduced in individuals with RTT (versus DD). These findings underscore the importance of correcting for global volume abnormalities when assessing regional volumetry and suggest that neuroimaging evaluations may distinguish children with RTT from those with idiopathic DD.
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4. Ma Y, Yang R, Yan X, Song X, Zhan F. Genetic analysis and prenatal diagnosis of 15q11-q13 microduplication syndrome. J Matern Fetal Neonatal Med. 2025; 38(1): 2505752.
OBJECTIVE: 15q11-q13 microduplication syndrome, a genetic disorder caused by duplications in the 15q11-q13 region, has been associated with autism spectrum disorder (ASD); however, research on chromosome 15 microduplications is scarce. We explored the copy number variant (CNV) characteristics of 15q11-q13 microduplication syndrome, pathogenic mechanisms of ASD-related causative genes in this region, and factors affecting ASD development. METHODS: We performed laboratory investigations and data collection on seven cases of 15q11-q13 microduplications, comprising 5 prenatal and 2 postnatal cases, detected using chromosomal microarray analysis (CMA), comparing their CNV characteristics and clinical presentations. RESULTS: Chromosomal karyotyping was not performed in one case, while the results for the others were normal. CMA revealed one case each of a microduplication at 15q11.2q13.3, 15q11.2, 15q13.2q13.3, 15q13.3, and three at 15q11.2q13.1, varying in size from 444 kb to 9.6 Mb. Of the seven confirmed cases, postnatal facial anomalies were present in two male patients (cases 5 and 6), with one exhibiting intellectual disability, speech delay, ASD features, and hypotonia. No significant abnormalities could be observed in the five female patients. Concerning the five prenatal cases, four exhibited an ultrasound testing suggestive of abnormality, one displayed no abnormality on the ultrasound, although the mother of the fetus had a history of adverse pregnancy outcomes. Finally, only case 5 displayed facial deformities after birth. The remaining four fetuses did not retain any abnormality during postnatal follow-up. » CONCLUSION: The 15q11-q13 region may be associated with an increased ASD risk, and its clinical phenotype may be related to sex. Our study presents detailed clinical features and molecular genetic data, providing important insights into the link between 15q duplications and ASD and diagnosing and treating the syndrome.
