Largely unaffected auditory and visual sensory processing phenotypes in the evoked potentials of Fmr1 KO2 mice

Abstract

Sensory sensitivity symptoms are common in autism spectrum disorders and fragile X syndrome. Mainly in the auditory modality, disturbed processing has been found in both fragile X patients and the corresponding genetic mouse model, the Fmr1 knockout mouse. Here, we tried to replicate the auditory deficits and assess whether also visual processing is affected, using electroencephalography readouts under freely behaving conditions in the second-generation Fmr1 knockout mice. No differences between wild-type and knockout animals were found in single auditory and visual evoked potentials in response to pure sine tones and full-field light flashes. Visual sensory gating was enhanced in the early but not the late components of the evoked potentials, but no changes were found in auditory sensory gating. The higher harmonics of the synchronisation response to flickering visual stimuli seemed to be reduced with 10, but not 20 or 40 Hz, stimulation. However, this effect was not reproduced in an independent second cohort of animals. No synchronisation differences were

Assessment of the excitation–inhibition ratio in the Fmr1 KO2 mouse using neuronal oscillation dynamics

“…2020 ; Kat et al. 2021 ; Kat and Kas 2022 ). Deoxyribonucleic acid for genotyping was extracted from ear clips using a lysis buffer (100 mM Tris pH 8.0, 200 nM NaCl, 5 nM ethylenediaminetetraacetic acid) with proteinase K (0.2 mg/ml).…”

“…EEG recordings were performed between 15 and 27 (experiment 1) or 10 and 13 (experiment 2) wk of age. Before the first resting-state recording animals were tested in auditory and visual ERP paradigms which have been published elsewhere ( Kat and Kas 2022 ).…”

Validating brain activity measures as reliable indicators of individual diagnostic group and genetically mediated sub-group membership Fragile X Syndrome

“…Further, preclinical models have highlighted speci c cell types [17,18]and brain structures [19] that may underlie these auditory chirp oscillatory abnormalities, and thus may serve as good targets for pharmacological intervention. Additional preclinical work has suggested that these phenotypes are speci c to the auditory modality [20], further narrowing the eld of inquiry to manageable outcomes. Of interest, many of the novel pharmaceuticals that have showed improvements in the chirp oscillatory phenotype in FMR1 KO mice are not targeted directly at the mGluR theory of FXS, but rather at alternative pathways such as endocannabinoid effects [16] and PDE10A inhibition [15].…”