Early postnatal expression of proteins associated with inhibitory synapses in the auditory brainstem

Abstract

<p>The lateral superior olive (LSO) is a binaural nucleus that is critical for azimuthal sound localization. Bipolar principal cells of the LSO compute interaural level differences (ILDs) by comparing converging excitatory and inhibitory inputs driven by either ear. More specifically, this computation relies on integrating excitatory inputs from the ipsilateral cochlear nucleus with inhibitory, GABA/glycinergic inputs from the medial nucleus of the trapezoid body (MNTB), which are driven by sound originating at the contralateral ear. In order to reliably compute ILDs, the converging inputs must represent sounds of the same frequency. This specificity emerges during the first few weeks of postnatal life in rats as a result of functional and anatomical refinement. Interestingly, significant refinement of this auditory circuit occurs in the absence auditory experience. We focused on changes in the subcellular location of MNTB inputs and the expression of vesicular proteins before hearing onset.</p> <p>The subcellular distribution of inputs onto a neuron heavily influences synaptic integration and the mature distribution likely emerges during a period of circuit refinement. Little is known about how the inputs are distributed onto LSO principal cells and how the mature distribution is achieved. We studied the distribution of inhibitory inputs onto LSO neurons and found that significant re- distribution occurs before hearing onset. The mechanisms underlying the refinement of the inhibitory MNTB projection are not well understood but could be related to the transient co-transmission of the excitatory neurotransmitter glutamate. We studied the expression of vesicular proteins that may regulate the release of GABA/glycine and glutamate at the immature MNTB terminal. We found that MNTB terminals transiently express two Ca++ sensors, which may be associated with the different release properties for GABA/glycine and glutamate. Lastly, we asked one specific example of what controls the expression and sorting of vesicular proteins at the immature MNTB terminal.</p>