Translation-relevant EEG phenotypes in a mouse Syndrome

NEUROBIOLOGY OF DISEASE

卷:115

Article

Lovelace, Jonathan W.¹  Ethell, Iryna M.^2,3  Binder, Devin K.^2,3  Razak, Khaleel A.^1,2 

[1] Univ Calif Riverside, Dept Psychol, 900 Univ Ave, Riverside, CA 92521 USA

[2] Univ Calif Riverside, Neurosci Grad Program, Riverside, CA 92521 USA

[3] Univ Calif Riverside, Div Biomed Sci, Sch Med, Riverside, CA 92521 USA

关键词: Fragile X Syndrome;    Autism;    Auditory cortex;    Sensory hypersensitivity;    Frontal cortex;    EEG;    Neural oscillations;   

DOI  :  10.1016/j.nbd.2018.03.012

来源: Elsevier

【 摘 要 】

Identification of comparable biomarkers in humans and validated animal models will facilitate pre-clinical to clinical therapeutic pipelines to treat neurodevelopmental disorders. Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety, social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include enhanced resting state gamma power and reduced inter-trial coherence of sound evoked gamma oscillations. To determine if analogous phenotypes are present in an animal model of FXS, we recorded EEGs in awake, freely moving Fmr1 knock out (KO) mice using similar stimuli as in the human studies. We report remarkably similar neural oscillation phenotypes in the Fmr1 KO mouse including enhanced resting state gamma power and reduced evoked gamma synchronization. The gamma band inter-trial coherence of neural response was reduced in both auditory and frontal cortex of Fmr1 KO mice stimulated with a sound whose envelope was modulated from 1 to 100 Hz, similar to that seen in humans with FXS. These deficits suggest a form of enhanced 'resting state noise' that interferes with the ability of the circuit to mount a synchronized response to sensory input, predicting specific sensory and cognitive deficits in FXS. The abnormal gamma oscillations are consistent with parvalbumin neuron and perineuronal net deficits seen in the Fmr1 KO mouse auditory cortex indicating that the EEG biomarkers are not only clinically relevant, but could also be used to probe cellular and circuit mechanisms of sensory hypersensitivity in FXS.

【 授权许可】

Free