| Abstract No.: | B-A2012 |
| Country: | Canada |
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| Title: | THE MORPHOLOGICAL DEVELOPMENT OF THE MOUSE CALYX OF HELD-MNTB SYNAPSE |
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| Authors/Affiliations: | 1 Giovanbattista Grande*; 1 Lu-Yang Wang;
1 Hospital for Sick Children, Toronto, ON, Canada
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| Content: | During the critical period of development, synaptic connections between neurons within the central nervous system are in a heightened state of plasticity. Initial connections are primarily driven by intrinsic genetic programs however sensory experience during the critical period of development refines and strengthens synapses. In the auditory circuits of the brainstem, ventral cochlear neurons give rise to a large glutamatergic terminal known as the calyx of Held. This synaptic terminal, which plays a pivotal role in sound localization, innervates a single principle neuron of the contralateral medial nucleus of the trapezoid body (MNTB). Our lab and others have shown that during the first 3 weeks of postnatal development, the calyx of Held-MNTB synapse undergoes profound biophysical transformations. For example, after auditory experience onsets around P11/12, presynaptic action potentials are markedly shortened and neurotransmitter release becomes more efficient, while excitatory postsynaptic currents display faster kinetics. As a consequence, the mature calyx of Held-MNTB synapse can transmit high-frequency signals with exceptional fidelity. Despite significant progress made, it is presently unclear how the physiological changes are coupled to the morphological maturation of synapses. The goal of this study is to characterize the morphology of the calyx of Held-MNTB synapse at different developmental stages; in particular, before and after the onset of hearing. Using paired recording methods in mouse brainstem slices, different coloured fluorescent tracers were loaded into the calyx of Held terminal and the MNTB neuron it innervates. Following histological processing, confocal microscopy was used to acquire z-stack images (1 micron thickness) of the entire calyx of Held-MNTB synapse and reconstruction software was used to render the synapse in 3D. Our preliminary results demonstrate striking morphological differences between immature (P7-P10) and mature (P16-P18) calyx of Held-MNTB synapses. At P7, only a small percentage of the MNTB neuron is contact with the calyx of Held terminal and the terminal appears flattened following the contour of the MNTB neuron. Also, the terminal has a much smaller volume and surface area. Conversely, at P17 a much larger percentage of the MNTB neuron is covered by the calyx of Held terminal and the volume and surface area of the terminal are larger. Rather than appear as a flattened structure, the terminal at P17 is digitated. Our results demonstrate that the morphology of the calyx of Held-MNTB synapse is highly dynamic during the first 3 weeks of postnatal development. It is likely that auditory experience, which begins to manifest around P11/12, triggers the mechanisms responsible for the physiological and morphological maturation of the calyx of Held-MNTB synapse. |
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