News Release

Neurobiology -- tuning of timing in auditory axons

Peer-Reviewed Publication

Ludwig-Maximilians-Universität München

This news release is available in German.

An LMU team has shown that the axons of auditory neurons in the brainstem which respond to low and high-frequency sounds differ in their morphology, and that these variations correlate with differences in the speed of signal conduction.

As a rule, the axons (i.e. signal-transmitting fibers) of the neurons in the central nervous systems of vertebrates are ensheathed in layers of myelin, which serves as a form of insulation that improves their electrical conduction properties. In fact, the fat-rich myelin coating largely consists of the cell membranes of so-called glia cells, which wrap themselves around the axon. Along the axons, the myelin sheath is regularly interrupted by structures referred to as the nodes of Ranvier, and its insulating effect ensures that action potentials can be built up (i.e. signal transmission can occur) only at these sites. In other words, the action potentials in myelinized axons propagate in a saltatory fashion, jumping from node to node across the intervening insulated stretches or 'internodes'. It has generally been assumed that the speed of conduction of action potentials along such axons increases with axon diameter and with the distance between successive nodes of Ranvier. A new study done by a team of researchers led by LMU neurobiologist Professor Benedikt Grothe, in collaboration with colleagues based at University College London, has now overturned this idea ­- which is cited in most neurobiology textbooks. "Our findings clearly refute the conventional notion that the speed of signal transmission in the myelinized axon of vertebrate neurons always increases in proportion to the length of the internodes," says Grothe. The new results appear in the latest issue of the online journal Nature Communications.

Our sense of hearing is dependent on the conversion of incoming mechanical oscillations into electrical impulses by the sensory hair cells in the inner ear. The impulses are then relayed by other neurons for further processing, which itself depends on the structural characteristics of the signal-transmitting axons. Since both ears encode a given acoustic stimulus in the same way, the decisive cues for sound localization arise from the fact that a given sound both arrives earlier at, and is perceived as louder by the 'ipsilateral ear' (the one closer to the sound source) than the stimulus that reaches the 'contralateral' ear. Hence, precise communication of the timing difference between the responses of the two ears to a given sound to higher processing centers is crucial for accurate localization of the sound source. For this reason, the brain must be capable of encoding minimal differences between the arrival times of signals at the two ears. This computation requires a complex set of interactions between the several different nerve cells that relay this information, in the form of action potentials, from the inner ear to auditory neurons in the brainstem.

Grothe and his colleagues have unexpectedly discovered that structural adaptations relating to the nodes of Ranvier and the intervening internodes in the auditory neurons in the mammalian brainstem play a critical role in tuning the rate and precision of signal propagation via these pathways.

Precise modeling of axonal geometry

"Our investigation revealed structural differences in the pattern of myelinization of their axons. The axons that are most sensitive to low-frequency tones are larger in diameter than those that respond to high-frequency sounds but ­- surprisingly ­- their internode regions are actually shorter," Grothe explains. In addition, computer simulations carried out by the researchers indicated that these variations in axon morphology should act to tune the speed of signal conduction. Subsequent electrophysiological measurements then confirmed that axons that react to low-frequency tones transmit signals faster and with greater fidelity.

"Our findings also contradict the widespread assumption that axons which serve the same function must be structurally identical, and that the length of their internodes is always proportional to the axon diameter," Grothe points out. "Instead, it looks as if there are systematic structural differences between them that depend on the site of origin of the signals and the nature of their target circuits." (Nature Communications 2015)


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