Calyx of Held

The Calyx of Held is a particularly large synapse in the mammalian auditory central nervous system, so named by Hans Held in his 1893 article Die centrale Gehörleitung because of its resemblance to the calyx of a flower. Globular bushy cells in the anteroventral cochlear nucleus (AVCN) send axons to the contralateral medial nucleus of the trapezoid body (MNTB), where they synapse via these calyces on MNTB principal cells. These principal cells then project to the ipsilateral lateral superior olive (LSO), where they inhibit postsynaptic neurons and provide a basis for interaural level detection (ILD), required for high frequency sound localization. This synapse has been described as the largest in the brain. The Calyx of Held is a particularly large synapse in the mammalian auditory central nervous system, so named by Hans Held in his 1893 article Die centrale Gehörleitung because of its resemblance to the calyx of a flower. Globular bushy cells in the anteroventral cochlear nucleus (AVCN) send axons to the contralateral medial nucleus of the trapezoid body (MNTB), where they synapse via these calyces on MNTB principal cells. These principal cells then project to the ipsilateral lateral superior olive (LSO), where they inhibit postsynaptic neurons and provide a basis for interaural level detection (ILD), required for high frequency sound localization. This synapse has been described as the largest in the brain. The related endbulb of Held is also a large axon terminal smaller synapse (15-30 µm in diameter) found in other auditory brainstem structures, namely the cochlear nucleus. As with the calyces, these synapses promote fast, efficient information transfer. The calyx of Held holds vesicles containing glutamate on the presynaptic terminal, the vesicles are released upon stimulation (originating in the auditory system). The glutamate then binds to two known glutamate receptors, AMPA- and NMDA receptors. Commonly used in research due to its large size, the calyx of Held has been used to understand a variety of mechanisms related to development of, and vesicle release of the synapse. The calyx of Held is a part of the auditory system, connecting the globular bushy cells (GBCs) of the anteroventral cochlear nucleus to the principal neurons of the medial nucleus of the trapezoid body (MNTB). As a synapse, the function of the calyx of Held is to transmit the signal from the GBCs to the principal neurons. The principal neurons of the MNTB are glycinergic, thus hyperpolarizing the superior olivary complex (SOC) nuclei in nearby cells and producing tonotopic inhibitory effects. As a result of its role in stimulating the principal neurons, the primary function of the calyx of Held is to allow differentiation between temporal activation of the cochlear hair cells that are important in sound localization (interaural level detection). Interaural level detection is possible through the calyx system due to the large relative size of the GBCs, the calyx of Held, and the principal neurons. The neurons in the Lateral Superior Olive are especially important in discerning these interaural level changes. The large diameter size of the bushy cell axons allows the inhibitory signal produced by the MNTB neurons to reach the SOC approximately 0.2 ms following the initial cochlear excitation. This ~0.2 second time measurement is important for comparing the contralateral (opposite side) and ipsilateral (same side) stimulation necessary in sound localization in the horizontal plane, and is key in distinguishing the location of low frequency sounds. For every principal neuron there is one calyx, and for most GBC axons there is only a single calyx, although there are exceptions to this pairing. This in general creates a one-to-one ratio between GBCs, the calyces of Held, and the principal neurons. The calyx of Held encompasses the principal neuron with a distinct morphology: branching of the calyx allows the creation of second- and third-order networks. Each branch establishes a connection with the principal neuron, establishing a large number of active zones. This is unusual for synaptic terminals in the brain, as most create a single active zone. Each calyx contains anywhere from 300 to 700 active zones, and in each of the active zones there are about 100 glutamate-containing vesicles with about 3 docked vesicles at a time. These vesicles are large, consistent with the findings regarding quantal size in other adult synapses. Dense-core vesicles, usually containing neuropeptides, are also present, but further research is needed to determine their content and function. To maintain the structure of the synapse, as with other synapses, there are many microtubules. The calyx has a large number of microtubules at the base of the terminal. These microtubules carry out a variety of functions, such as providing stability to the synapse, restricting the distribution of the synaptic vesicles, and localizing the mitochondria. Mitochondria have three important functions at the synaptic terminal: allowing the synapse to meet metabolic needs (especially for removal of calcium after depolarization), buffering the calcium by allowing uptake of calcium into the mitochondria, and providing energy for glutamate synthesis. Various glial cells are also associated with the calyx of Held. Two types of glial cells surround the calyx: astrocytes and NG2 glial cells. The astrocytes express glutamate transporters to remove glutamate from the synapse. This is the only known mechanism for removal of glutamate from the synapse. The NG2 glial cells express AMPA receptors.