In vestibular sensory epithelia such as the macula of the utricle (A), a simple sensory map comprising two zones (striola vs. extrastriola) provides natural access to basic questions of how hair cells and afferent neurons generate, transmit, and propagate sensory signals. Utricular hair cells (B, type I and type II) transduce linear head accelerations and head tilt into receptor potentials, which drive transmission across highly specialized calyx and bouton terminals of utricular afferent neurons (B). Postsynaptic responses in the afferent terminals initiate patterns of action potentials (spike trains) at hemi-nodes, which propagate along the vestibular nerve through bipolar cell bodies (VGN) in the vestibular ganglion 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. 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 electrical signals from individual hair cells, afferent terminals, and neuronal cell bodies in intact rodent vestibular epithelia.
Several of our ongoing investigations (see Current Projects) concern the roles of specialized ion channels in synaptic transmission mechanisms (C). Synaptic transmission involves both quantal transmission: glutamate release from synaptic vesicles clustered at presynaptic ribbons, and novel non-quantal transmission at the synapse between type I hair cells and afferent calyces. Non-quantal transmission occurs by fast positive ion 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+ level in the extended synaptic cleft.
We are also investigating how differential expression of ion channels contributes to zonal differences in the regularity of spike timing (A). 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.
We also collaborate with other groups to study:
the nature of synaptic transmission at the unique type I hair cell-calyx synapse – Aravind Chenrayan Govindaraju, Rob Raphael (Rice), Anna Lysakowski (UIC)
how different hair cell types acquire their identities – 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” doi.org/10.1523/JNEUROSCI.3127-20.2021, in collaboration with Jenny Stone, Rémy Pujol, and Connor Finkbeiner (University of Washington)
how the epithelial sensory map is specified in zones and hair bundle polarity – Doris Wu (NIDCD), Kathy Cullen (Johns Hopkins), Basile Tarchini (The Jackson Laboratory).