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J Comp Neurol. 2017 Nov 1;525(16):3543-3562. doi: 10.1002/cne.24290. Epub 2017 Aug 15.

Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid body in a mouse model of Fragile X syndrome.

Author information

1
Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, Colorado.
2
Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.
3
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
4
Department of Pediatrics, School of Medicinen University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Abstract

Hyperexcitability and the imbalance of excitation/inhibition are one of the leading causes of abnormal sensory processing in Fragile X syndrome (FXS). The precise timing and distribution of excitation and inhibition is crucial for auditory processing at the level of the auditory brainstem, which is responsible for sound localization ability. Sound localization is one of the sensory abilities disrupted by loss of the Fragile X Mental Retardation 1 (Fmr1) gene. Using triple immunofluorescence staining we tested whether there were alterations in the number and size of presynaptic structures for the three primary neurotransmitters (glutamate, glycine, and GABA) in the auditory brainstem of Fmr1 knockout mice. We found decreases in either glycinergic or GABAergic inhibition to the medial nucleus of the trapezoid body (MNTB) specific to the tonotopic location within the nucleus. MNTB is one of the primary inhibitory nuclei in the auditory brainstem and participates in the sound localization process with fast and well-timed inhibition. Thus, a decrease in inhibitory afferents to MNTB neurons should lead to greater inhibitory output to the projections from this nucleus. In contrast, we did not see any other significant alterations in balance of excitation/inhibition in any of the other auditory brainstem nuclei measured, suggesting that the alterations observed in the MNTB are both nucleus and frequency specific. We furthermore show that glycinergic inhibition may be an important contributor to imbalances in excitation and inhibition in FXS and that the auditory brainstem is a useful circuit for testing these imbalances.

KEYWORDS:

RRID: AB_1587626; RRID: AB_2278725; RRID: AB_2619997; brain stem; fragile X syndrome; gamma-aminobutyric acid; glutamic acid; glycine; sound localization

PMID:
28744893
PMCID:
PMC5615817
DOI:
10.1002/cne.24290
[Indexed for MEDLINE]
Free PMC Article

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