The vestibular inner ear: Mechanotransduction, synaptic transmission, and afferent encoding

The vestibular inner ear encodes head motion and position in signals initiated and shaped by mechanosensitive and voltage-gated ion channels of sensory receptor cells (hair cells), transmitted by extraordinary mechanisms to afferent neurons, and translated into spike trains by voltage-gated ion channels at spike initiation zones adjacent to the afferent terminals.  Signals from central and peripheral  zones on the sensory epithelium are shaped differentially by distinct complements of ion channels in both hair cells and afferent neurons.

To analyze the transformation of sensory signals by ion channels at each processing stage, we use the whole-cell method of patch clamping to record currents and voltages from individual hair cells, afferent terminals, and neuronal cell bodies in intact rodent vestibular epithelia.  The stimuli are controlled deflections of the mechanosensitive hair bundles and voltage or currents injected through the recording pipette.

A, In the sensory epithelium of the rodent utricle, a simple sensory map of two zones (a central striola and surrounding extrastriola, ES) provides natural access to basic questions of how hair cells and afferent neurons generate, transmit, and propagate sensory signals.  The polarity of hair bundles reverses at the lateral edge of the striola (line of polarity reversal, LPR).

We are investigating how the differential expression of ion channels in both hair cells and afferent neurons contributes to zonal differences in the regularity of spike timing.  Striolar afferents use irregular spike timing to encode large, rapid head motions and vibrations, whereas extrastriolar afferents use highly regular spike timing to encode smaller and slower changes in  head position.

  • Differences in spike timing regularity reflect systematic differences in expression of voltage-gated K channels and, possibly, sodium (Na) channels (see Selina Baeza-Loya’s Current project).

B, Utricular hair cells of 2 types (HCI and II) transduce linear head accelerations and head tilt into receptor potentials, which drive transmission across highly specialized calyx and bouton afferent terminals.  Postsynaptic responses in the afferent terminals arrive at hemi-nodes where they initiate spike trains that propagate along the nerve fibers through cell bodies (vestibular ganglion neurons, VGNs) and on to central targets in the brainstem and cerebellum.  These afferent signals contribute to our sense of heading and drive fast, accurate reflexes that stabilize vision and balance as we move.

C, Several current projects concern the roles of specific ion channels in synaptic transmission mechanisms at the synapse between HCI and afferent calyx terminals.  These synapses use both quantal transmission: glutamate release from synaptic vesicles clustered at presynaptic ribbons, and novel non-quantal transmission.

  • Computational analysis from our collaboration with the Raphael and Lysakowski labs (below) suggests that non-quantal transmission occurs by fast current flow through open low-voltage-activated ion channels in both the pre-synaptic hair cell membrane (K,L channels) and post-synaptic calyx membrane (Kv1, Kv7, HCN), and by slower modulation of K+ concentration in the extended synaptic cleft. 
  • See Hannah Martin’s current project on the molecular nature of the unusual low-voltage-activated K conductance (gK,L) in HCI. 

Collaborations with other groups:

The nature of synaptic transmission at the unique HCI-calyx synapseAravind Chenrayan Govindaraju, Rob Raphael (Rice), Anna Lysakowski (UIC):  Govindaraju AC, Quraishi IH, Lysakowski A, Eatock RA, Raphael RM. A Biophysical Model of Nonquantal Transmission at the Vestibular Hair Cell-Calyx Synapse: KLV currents Modulate Fast Electrical and Slow K+ potentials in the Synaptic Cleft.  BioRXiv,

How different hair cell types acquire their identitiesAntonia (Toni) González Garrido and  Omar López Ramírez with Jenny Stone (University of Washington), Brandon Cox (SIU), Neil Segil (USC) –  see “The differentiation status of hair cells that regenerate naturally in the vestibular inner ear of the adult mouse”, in  collaboration with  Jenny Stone, Rémy Pujol, and Connor Finkbeiner (University of Washington).  See current projects by Antonia (Toni) González Garrido

How epithelial zones and maps of hair bundle polarity are specified – Kazuya Ono, Omar López Ramírez, with  Doris Wu (NIDCD), Kathy Cullen (Johns Hopkins), Basile Tarchini (The Jackson Laboratory)