25508
Alteration in EEG and Auditory Evoked Potential in a Mouse Model of Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is a rare genetic disorder associated with autism spectrum disorder (ASD) in approximately 50% of cases, making it one of the most common genetic forms of autism. Dysregulation of the mTOR pathway in TSC results in alterations in axon outgrowth and synapse formation similar to many other autism related mutations. TSC, therefore, can be used as a model of autism related synaptopathy. The consequences of synaptopathy can be explored at the systems level through the measurement of neural activity via electroencephalography (EEG). Spectral power and evoked potentials measured from EEG can be used to quantify neural activity in both patients with TSC and in mouse models of Tscmutation. Altered patterns of neural activity could be used as a translational, quantitative biomarker for the development of novel therapeutics.
Objectives:
To characterize auditory evoked potential and resting state EEG in a transgenic mouse model of TSC for use as a translational biomarker of synaptic function.
Methods:
Neural activity was measured using a wireless, telemeterized EEG recording system from mice expressing a hypomorphic Tsc2allele under control of a neuronal specific promoter. Electrical activity was recorded from a screw located over the frontal lobe. Spectral power from resting state EEG and auditory evoked potential elicited from a mismatch negativity paradigm were collected.
Results:
Mice with reduced expression of Tsc2have a reduction in oscillatory power in low frequency bands (theta) but an increase in power in the high frequency bands (beta and gamma). Mutant animals also have an alteration in the evoked response to auditory tones relative to control animals.
Conclusions:
The resting state and evoked changes in neural activity in the Tsc2 mutant mouse could be used as a biomarker of alterations in brain connectivity underlying behavioral impairments. Comparison of the effect of pharmacological treatments on behavioral and neurophysiological measures in rodents and patients could enable the use of EEG as a translational biomarker of treatment efficacy.