ABSTRACT
Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30-80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome.
Subject(s)
Baclofen/pharmacology , Evoked Potentials, Auditory/drug effects , Fragile X Syndrome/complications , GABA-B Receptor Agonists/pharmacology , Mental Disorders/etiology , Mental Disorders/pathology , Acoustic Stimulation , Animals , Disease Models, Animal , Electroencephalography , Evoked Potentials, Auditory/genetics , Exploratory Behavior/drug effects , Exploratory Behavior/physiology , Female , Fragile X Mental Retardation Protein/genetics , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/genetics , Interpersonal Relations , Male , Maze Learning/drug effects , Memory, Short-Term/drug effects , Memory, Short-Term/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Spectrum AnalysisABSTRACT
We describe a wave-mechanical implementation of classically chaotic n-disk scattering based on thin two-dimensional microwave cavities. Two-, three-, and four-disk scatterings are investigated in detail. The experiments, which are able to probe the stationary Green's function of the system, yield both frequencies and widths of the low-lying quantum resonances. The observed spectra are found to be in good agreement with calculations based on semiclassical periodic orbit theory. Wave-vector autocorrelation functions are analyzed for various scattering geometries, the small wave-vector behavior allowing one to extract the escape rate from the quantum repeller. Quantitative agreement is found with the value predicted from classical scattering theory. For intermediate energies, nonuniversal oscillations are detected in the autocorrelation function, reflecting the presence of periodic orbits.
ABSTRACT
Quantum and classical correlations are studied experimentally in model n-disk microwave billiards. The wave vector kappa autocorrelation C(kappa) of the quantum spectrum displays nonuniversal oscillations for large kappa, comparable to the universal random matrix theory behavior observed for small kappa. The nonuniversal behavior is shown to be completely determined by the classical Ruelle-Pollicott resonances, arising from the complex eigenvalues of the Perron-Frobenius operator, and calculated using periodic orbit theory. This work establishes a fundamental connection between the quantum and classical correlations of an open system.
