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Ruth Anne Eatock, Ph.D.
Professor of Otology and Laryngology and Neurobiology, Harvard Medical School

eatock@meei.harvard.edu

Lab website: http://eatocklab.tumblr.com/

Biophysical studies of receptor cells and neurons in the mammalian inner ear

The receptor cells of the inner ear are called hair cells after their conspicuous bundles of fine, hair-like, processes (see cartoon in Fig. 2).  Hair cells transduce sound and head motions into electrical signals, which they transmit across synapses to afferent neurons, which in turn carry the electrical signals from the inner ear to the brain.  We study all three stages in the inner ear:  sensory transduction within the hair cell; synaptic transmission from hair cell to afferent neuron,  and the generation of neural firing patterns that carry different kinds of information.  To make and shape their sensory signals, hair cells and afferent neurons use diverse ion channels.   We investigate how the properties of specific ion channels shape sensory signals.  For example, low-voltage-activated potassium (K) channels in certain vestibular hair cells and afferents improve the speed of sensory signaling and may be critical to the fidelity of vestibular reflexes. 

In addition to their value as models of signal transfer in the nervous system, the hair cells and afferent neurons of the inner ear are clinically significant.  Noise, drugs and the accumulated effects of aging affect transduction and synaptic transmission in the inner ear, leading to sensorineural hearing loss and an inability to maintain gaze and balance.  Thus, knowing how hair cells and neurons create and transfer signals is important for the therapy of damaged ears. 

Our principal model preparations have been the sensory epithelia of the rodent utricle (Figure 1) and  saccule, which sense linear head movements and head tilt.  These have unusual synaptic diversity: afferent neurons form large cup-shaped synaptic endings (calyces) on type I hair cells, as shown in Figure 2, and more conventional small (bouton) endings on type II hair cells.

Figure 1: Whole mount of part of the mouse vestibular labyrinth, illustrating the tissues that we study in vitro (from Dr. Jingbing Xue). Shown are the hair cell epithelia of the anterior and lateral semicircular canals and the utricle., as well as the vestibular ganglion and distal nerve branch connecting the ganglion to the epithelia.   Some ganglion cell bodies are brightly stained with labeled antibody to calretinin, a calcium binding protein.

We use the whole-cell patch clamp recording method to characterize the electrical responses of the sensory cells to sensory stimulation. Figure 2 illustrates examples of transduction currents (Imet) and receptor potentials (Vrec) of a hair cell and action potentials from an afferent ending (calyx stalk spikes), all evoked by deflection of the hair bundle (top trace) by a stimulus probe at different frequencies from 2 to 200 Hz . We also use molecular methods to identify the ion channels, and modeling to identify the functional significance of distinctive ion channel properties, gradually building an understanding of how inner ear organs process sensory stimuli.

Figure 2: Responses of a hair cell and a calyceal afferent terminal to sinusoidal deflections of the hair bundle. Right, A type I hair cell and its afferent terminal, showing the locations of the stimulus probe (against the hair bundle) and two recording pipettes, one on the hair cell and one on the afferent calyx ending. Various ion channels in the hair cell and afferent ending are indicated, including the mechanosensitive channels of the hair bundle (met) and potassium channels in the basolateral hair cell membrane (DR; KCNQ; K,L). Left, top trace, The bundle was deflected with sinusoidal bursts from 2 Hz to 200 Hz. Middle traces (Imet and Vrec), the transduction current and receptor potential evoked in the hair cell. Bottom traces, Action potentials recorded with a loose-patch recording from a calyx stalk.


Publications

1. Rüsch A, Lysakowski A, Eatock RA (1998) Postnatal development of type I and type II hair cells in the mouse utricle: Acquisition of voltage-gated conductances and differentiated morphology. J Neurosci 18: 7487-7501.

2. Chen JW-Y, Eatock RA (2000) A major potassium conductance in type I hair cells from rat semicircular canals: Characterization and modulation by nitric oxide. J Neurophysiol 84: 139-151.

3. Vollrath MA and Eatock RA (2003) Time course and extent of mechanotransducer adaptation in mouse utricular hair cells: Comparison with frog saccular hair cells. J Neurophysiol 90:2676-2689.

4. Wong W-H, Hurley KM and Eatock RA. (2004) Differences in the negatively inactivating potassium conductances of mammalian cochlear and vestibular hair cells. J Assoc Res Otolaryngol 5:270-84.

5. Hurley KM, Gaboyard S, Zhong M, Price SD, Wooltorton JRA, Lysakowski A, Eatock RA (2006) M-like K+ currents in type I hair cells and calyx afferent endings of the developing rat utricle. J Neurosci 26:10253-10269.

6. Wooltorton JRA, Gaboyard S, Hurley KM, Price SD, Bao H, Garcia JL, Lysakowski A, Eatock RA (2007) Developmental changes in two voltage-dependent sodium currents in utricular hair cells. J Neurophysiol 97:1684-1704.

7. Kalluri R, Xue J, Eatock RA. (2010) Ion channels set spike timing regularity of mammalian vestibular afferent neurons. J Neurophysiol. 104:2034-51.

8. Lysakowski A, Gaboyard-Niay S, Calin-Jageman I, Chatlani S, Price SD, Eatock RA.  (2011) Molecular microdomains in a sensory terminal, the vestibular calyx ending.  J Neurosci 31:10101-14  

Reviews

1. Eatock RA (2000) Adaptation in hair cells. Annu Rev Neurosci 23: 285-314.

2. Eatock RA, Hurley KM (2003) Functional development of hair cells. Curr Top Dev Biol 57:389-448.

3. Eatock RA, Lysakowski A (2006) Mammalian vestibular hair cells. In: Vertebrate Hair Cells (Eatock, Fay, Popper, eds.) Springer: New York, pp 348-442.

4. Eatock RA, Xue J, Kalluri R (2008) Ion channels in mammalian vestibular afferents may set regularity of firing. J Exp Biol 211:1764-1774.

5. Eatock RA, Songer JE (2011) Vestibular hair cells and afferents: Two channels for head motion signals.  Annu Rev Neurosci 34:501-34