Tuesday, April 23, 2024
4/23/2024
SUMMARY Vestibular and auditory afferent neurons are the primary conduits for information transfer from the sensory periphery to the brainstem. Many hearing and balance impairments are caused by death or damage to these neurons or their partner hair cells. In both vestibular and auditory afferents some functionally distinct neuronal sub-groups are more susceptible to damage than others. By understanding the mechanisms that shape the function of these sensory neurons, we hope to better understand why this is the case. We hypothesize that heterogeneity in the composition of neuronal ion channels is important for shaping their function. We base our hypothesis on the observation that the cell bodies of vestibular and auditory afferents are remarkably heterogeneous in their intrinsic firing patterns and ion channels. Previous studies could not reliably link ion channel properties to afferent function because the isolated cell bodies lacked the necessary morphological markers that would allow functional identification. To deal with this problem, we will perform patch-clamp recordings together with single cell labeling in semi-intact neuro-epithelium preparations in which neurons are still connected to their hair cells. We will link ion channel properties with neuronal function by exploiting established associations between function and patterns of afferent connectivity with hair cells. Combined with pharmacological manipulation of candidate ion channels and theoretical modeling, our experiments will test if and how specific groups of ion channels influence neuronal function. Alternatively, the approach will offer new candidate ion channels for consideration. These experiments will also contribute to our understanding of neuronal differentiation by mapping ion channel properties onto afferent connectivity during critical developmental periods when afferent innervation patterns are forming and stabilizing. By taking a developmental approach we will disentangle the significance of ion channel diversity as an indication of neuronal maturation versus its importance for adult function. Our focus on vestibular and auditory afferents within one study, using similar methodology, will reveal ion channel specializations that are unique to each system and specializations that are common across both systems. In defining how ion channels differ among functionally distinct neuronal groups, our work may identify the mechanisms that render some neurons more susceptible to damage, which could lead to pharmacological interventions for protecting vulnerable neuronal groups.
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