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Coherent Anti-Stokes Raman Spectroscopy (CARS) Application for Imaging Myelination in Brain Slices

Coherent anti-Stokes Raman spectroscopy (CARS) is a technique classically employed by chemists and physicists to produce a coherent signal of signature ...

University of Colorado Anschutz

The auditory brainstem compares sound-evoked excitation and inhibition from both ears to compute sound source location and determine spatial acuity. Although alterations to the anatomy and physiology of the auditory brainstem have been demonstrated in fragile X syndrome (FXS), it is not known whether these changes cause spatial acuity deficits in FXS. To test the hypothesis that FXS-related alterations to brainstem circuits impair spatial hearing abilities, a reflexive prepulse inhibition (PPI) task, with variations in sound (gap, location, masking) as the prepulse stimulus, was used on  knock-out mice and B6 controls. Specifically,  mice show decreased PPI compared with wild-type mice during gap detection, changes in sound source location, and spatial release from masking with no alteration to their overall startle thresholds compared with wild-type mice. Last,  mice have increased latency to respond in these tasks, suggesting additional impairments in the pathway responsible for reacting to a startling sound. This study further supports data in humans with FXS that show similar deficits in PPI.

Characterization of Auditory and Binaural Spatial Hearing in a Fragile X Syndrome Mouse Model.

Auditory symptoms are one of the most frequent sensory issues described in people with Fragile X Syndrome (FXS), the most common genetic form of intellectual disability. However, the mechanisms that lead to these symptoms are under explored. In this study, we examined whether there are defects in myelination in the auditory brainstem circuitry. Specifically, we studied myelinated fibers that terminate in the Calyx of Held, which encode temporally precise sound arrival time, and are some of the most heavily myelinated axons in the brain. We measured anatomical myelination characteristics using coherent anti-stokes Raman spectroscopy (CARS) and electron microscopy (EM) in a FXS mouse model in the medial nucleus of the trapezoid body (MNTB) where the Calyx of Held synapses. We measured number of mature oligodendrocytes (OL) and oligodendrocyte precursor cells (OPCs) to determine if changes in myelination were due to changes in the number of myelinating or immature glial cells. The two microscopy techniques (EM and CARS) showed a decrease in fiber diameter in FXS mice. Additionally, EM results indicated reductions in myelin thickness and axon diameter, and an increase in g-ratio, a measure of structural and functional myelination. Lastly, we showed an increase in both OL and OPCs in MNTB sections of FXS mice suggesting that the myelination phenotype is not due to an overall decrease in number of myelinating OLs. This is the first study to show that a myelination defects in the auditory brainstem that may underly auditory phenotypes in FXS.

Article	Year
Characterization of Auditory and Binaural Spatial Hearing in a Fragile X Syndrome Mouse Model. eNeuro\| PubMed ID: 31953317	2020
Myelination Deficits in the Auditory Brainstem of a Mouse Model of Fragile X Syndrome. Frontiers in neuroscience\| PubMed ID: 34858133	2021

Shani Poleg

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