Molecular physiology of signal transmission along the auditory pathway

by Tanvi Butola
Doctoral thesis
Date of Examination:2017-05-16
Date of issue:2017-12-13
Advisor:Prof. Dr. Tobias Moser
Referee:Prof. Dr. Erwin Neher
Referee:Prof. Dr. Thomas Dresbach
Persistent Address: http://dx.doi.org/10.53846/goediss-6529

 

 

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Abstract

English

Signal transmission lies at the core of brain function. Understanding how information is transferred from one neuron to the other is the first step toward deciphering not just normal brain processing but the pathology of a diseased brain. This thesis investigates the role of three proteins (Piccolo, Bassoon and RIM-BP2) that are crucial for the neurotransmitter release machinery and of the BEACH protein, LRBA2 that drew attention as a candidate to study sensory signal processing because of the hearing deficit reported in LRBA2 KO mice. Through a combination of in vitro and in vivo electrophysiology, and fluorescence imaging, this thesis studies the molecular physiology of signal transmission at the synapses in the central and peripheral auditory system. Piccolo and Bassoon were found to maintain vesicle replenishment, with Bassoon possibly having an additional role in regulating release probability at the central auditory synapse, the endbulb of Held. RIM-BP2 was indicated to be a key player in coupling presynaptic Ca2+ influx to the release of neurotransmitters, hence orchestrating ultrafast signal transmission at the endbulb of Held synapse. LRBA2 was found to be essential for proper hair bundle morphology of the sensory hair cells of the cochlea, and hence maintaining functional cochlear amplification and reliable transduction of the acoustic signal.
Keywords: Piccolo; Bassoon; RIM-BP; LRBA; Cochlea; endbulb of Held; Synaptic transmission; Short-term plasticity
 
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