Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
Last Name

Contact Us
If you have any questions or feedback please contact us.

Neurotransmission at the vestibular calyx synapse

Collapse Biography 

Collapse Overview 
Collapse abstract
The goal of this proposal is to understand synaptic transmission at the vestibular type I hair cell/calyx synapse. Three classes of morphological afferents have been described in the amniote crista and utricle. Calyx units contact type I hair cells (HCI) exclusively, bouton units contact type II hair cells only &dimorphic units receive innervation from both bouton &calyx fibers (Goldberg, 2000). The physiological response dynamics of these three classes of fibers vary, with calyx units having the most irregular firing pattern &the lowest gains to rotational stimuli (Baird et al. 1988;Lysakowski et al. 1995). The reasons for these variations are unclear, but are hypothesized to include differences in hair cell mechano-electrical transduction (MET) properties &differences in the biophysical membrane properties of primary vestibular afferents. We will study HCI &associated calyx afferents to determine how firing patterns in this unique terminal are shaped by both pre- &post-synaptic mechanisms. In Aim 1, patch clamp techniques will be used to study ionic conductances &transmitter release in a newly developed preparation of calyx terminals isolated together with HCI from gerbil vestibular organs (Rennie &Streeter, 2006). Excitatory postsynaptic currents (EPSCs) resulting from hair cell transmitter release will be recorded from calyx terminals under a variety of conditions. In Aim 2 we will record MET currents &receptor potentials from HCI during displacement of the hair bundle with a stiff probe in a wholemount utricle preparation. In Aim 3, mathematical modeling techniques will be employed to simulate HCI &calyx responses to glutamate. The passive electrical properties of the calyx &attached axon will be simulated with a segmented computational model in the NEURON programming environment. Na+, Ca2+ and K+ channels will be modeled with Hodgkin-Huxley style rate constants using the experimental data obtained in Aims 1&2. A genetic algorithm wiil be used to optimize the kinetic parameters for the activation &inactivation of ionic conductances. Dizziness is one of the most common medical complaints. Understanding the basic cellular mechanisms of balance sensation is essential to lay the groundwork for identifying causes &cures for this debilitating condition. The combination of experimental &modeling approaches will elucidate how sensory information is transformed by HC1 &converted into a neural code by their afferents.

Collapse sponsor award id

Collapse Time 
Collapse start date
Collapse end date

Copyright © 2024 The Regents of the University of Colorado, a body corporate. All rights reserved. (Harvard PROFILES RNS software version: 2.11.1)