Neurosciences

Ruili Xie, Ph.D.

ruili

Assistant Professor
Office: 186 Block Health Sciences Building
Tel: 419-383-6439
Lab: 419-383-4201 (HSB 108)
Fax: 419-383-3008
Email: ruili.xie@utoledo.edu

Education:
B.S.      1997    Peking University, Beijing, China
M.S.     2000    Institute of Genetics, Chinese Academy of Sciences, Beijing, China
Ph.D.   2006    University of Texas at Austin, Austin, TX

Research Interest:
Hearing loss becomes prevalent more than ever due to the steady increase of our life expectancy (leads to the increase in age-related hearing loss, or presbycusis), and over-exposure to sound from sources like personal electronic devices (leads to noise-induced hearing loss).  I study how the auditory nervous system processes sound, and how the neural processing is disrupted under aging and hearing loss conditions.  The primary goals of my research are to elucidate the mechanisms at the molecular, cellular and circuit levels that underlie normal hearing as well as hearing loss conditions due to aging and noise trauma.

Research Techniques:
Our studies primarily utilize whole-cell patch clamp recording technique to investigate the synaptic transmission in mouse brain slices.  We also combine other experimental approaches including pharmacology, immunohistology, molecular biology, optogenetics, and behavioral techniques in our research.

 Research Summary:

mice

The animal model of my research
Like people, mouse loses hearing during aging and after noise trauma.  They share the same mechanisms of auditory nervous system with us, yet are small and stable enough for breeding and experimental manipulations.  Various types of transgenic and mutant mice are readily available and more are being developed for the neuroscience research.  They are ideal to use in studying aging and hearing loss.  Picture shows three young mice at 1 month and an old one at 19 month.  

 

 
abr

Hearing test – (ABRs)
We assess mouse hearing by recording sound evoked auditory brainstem responses (ABRs).  Hearing loss is seen in aged mice(19 month) and mice with noise trauma, in terms of ABR waveform amplitude. Inset: example ABR waveform to a 70 dB SPL click. Red: young mouse (3 month); Green: aged mouse (19 month); blue: young mice with noise trauma (3 month).

 

 

The cochlear nucleus (CN)
An image of the cochlear nucleus from a mouse brain slice (left), and the diagram of a simplified CN neural circuit (right).  Different principal cell types in the CN process distinct aspects of the sound information.  For example, bushy cells encode the fine temporal information of the sound structure, which is critical for sound localization as well as the performance of complex auditory tasks like speech recognition.  The neural encoding of such fine temporal information is deteriorated during aging and hearing loss, which makes the bushy cells and the synapses they receive good targets of research.  Red lines: excitatory auditory nerve (AN) projections.  TBV: tuberculoventral cells that project glycinergic inputs to both bushy and T-stellate cells.  Three regions of the CN are AVCN (anteroventral CN), PVCN (posteroventral CN) and DCN (dorsal CN).

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Endbulb of Held synapses and bushy cells
Left: drawing of the endbulb of Held (by O’Neil et al, 2011) to show the giant synapse that wraps around the soma of the postsynaptic bushy cell. The synapse is specialized to faithfully transmit sound information with temporal precision.  Right: an example bushy cell patched during whole-cell recording. Cell was filled with Alexa Fluor 488 for visualization.

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Synaptic transmission is compromised during aging and hearing loss
Voltage-clamp recordings of EPSCs in bushy cells to stimulations of the endbulb of Held synapse. Notice that the synchronous EPSC responses were large and well-timed to the stimulus onset (tick marks on top), but were small and less well-timed in aged mice and mice with noise trauma. The asynchronous (or delayed) EPSC responses were rare in young mice, but increased a lot in aged and noise trauma mice. Both types of responses were partially rescued by bathing the slice in EGTA-AM in mice with noise trauma (Noise Trauma + EGTA), suggesting that presynaptic calcium levels are elevated under aging and hearing loss conditions.  Only the last 5 responses of the 50 pulse-train at 400 Hz were shown.

Optogenetic tools for the study of inhibitory mechanisms
Top: 2-photon image of the cochlear nucleus from a VGAT-EYFP-Channelrhodopsin-2 mouse, which express EYFP-ChR2 fusion protein in inhibitory neurons (VGAT positive neurons).   Red arrow: an inhibitory neuron with EYFP fluorescence under 2-photon excitation (975 nm wavelength).  Green arrows: shadow of non-EYFP-expressing cells (excitatory neurons, including bushy cells). Bottom: light stimulation (2-photon at 940 nm wavelength to excite ChR2) evoked spikes in ChR2 expressing inhibitory neurons, and evoked IPSPs in bushy cells that receive inputs from inhibitory neurons.

 

Research Grants:
NIDCD R01 grant, #R01DC016037: Cellular mechanisms of age related hearing loss (2017-2022, active).  Principal investigator: Ruili Xie.  Total award: $1,881,315 (Direct: $1,250,000; Indirect: $631,315).

NIDCD small research grant (R03), #R03-DC013396: Synaptic mechanisms underlying noise-induced and age-related hearing loss (2013-2017, completed).  Principal investigator: Ruili Xie. Total award: $456,000 (Direct: $300,000; Indirect: $156,000).

References:
1.   
Xie R, Manis PB.  Intrinsic excitability and synaptic properties of auditory nerve input of radiate and planar multipolar neurons in the mouse anteroventral cochlear nucleus.  Under review.

  2.    Xie R, Manis PB (2017).  Synaptic transmission at the endbulb of Held deteriorates during age-related hearing loss.  J Physiol 2017 Feb 1; 595(3):919-934.

  3.    Xie R.  Transmission of auditory sensory information decreases in rate and temporal precision at the endbulb of Held synapse during age-related hearing loss.  J Neurophysiol. 2016; 116(6):2695-2705.  Special issue: Auditory System Plasticity.

  4.    Xie R and Manis PB.  GABAergic and glycinergic inhibitory synaptic transmission in the cochlear nucleus studied in VGAT channelrhodopsin-2 mice.  Front Neural Circuits 2014 July 24;8:84.

 5.    Xie R and Manis PB.  Glycinergic synaptic transmission in the cochlear nucleus of mice with normal hearing and age-related hearing loss. J Neurophysiol. 2013 Oct; 110(8): 1848-1859.

 6.    Xie R and Manis PB.  Target-specific IPSC kinetics promote temporal processing in auditory parallel pathways.  J Neuroscience.  2013 January 23; 33(4): 1598-1614.  * Featured article in “This Week in The Journal.

7.    Rich AW, Xie R, and Manis PB.  Hearing loss alters quantal release at cochlear nucleus stellate cells.  Laryngoscope. 2010 Oct; 120 (10): 2047-53.

  8.    Pollak GD, Xie R, Gittelman JX, Andoni S, and Li N.  The dominance of inhibition in the inferior colliculus.  Hear Res. 2011 Apr; 274(1-2):27-39.

  9.    Pollak GD,Gittelman JX, Li N, and Xie R.  Inhibitory projections from the ventral nucleus of the lateral lemniscus and superior paraolivary nucleus create directional selectivity of frequency modulations in the inferior colliculus: A comparison of bats with other mammals.  Hear Res. 2011 Mar; 273(1-2):134-44.

 10.  Xie R, Gittelman JX, Li N, and Pollak GD.  Whole cell recordings of intrinsic properties and sound-evoked responses from the inferior colliculus.  Neuroscience. 2008 June 12; 154(1):245-56 (invited article on special issue).

 11.  Xie R, Gittelman JX, and Pollak GD.  Rethinking tuning: in vivo whole cell recordings of the inferior colliculus in awake bats.  J Neuroscience. 2007 Aug 29; 27(35):9469-81.

 12.  Xie R, Meitzen J. and Pollak GD.  Differing roles of inhibition in hierarchical processing of species-specific calls in auditory brainstem nuclei.  J Neurophysiol. 2005 Dec; 94(6):4019-37.

 13.  Xie R, Wan YF, Zhang Y and Wang DW.  HMW glutenin subunits in multiploid Aegilops species: composition analysis and molecular cloning of coding sequences.  Chinese Science Bulletin. 2001, 46 (4): 309-313.

 

Book Chapter:
Manis PB, Xie R, Wang Y, Marrs GS, and Spirou GA (2012).  The Endbulb of Held.  In: Springer Handbook of Auditory Research (Vol. 41): Synaptic Mechanisms in the Auditory System.  pp 61-93.  Edited by Trussell LO, Popper AN and Fay RR.  New York: Springer.

 For latest publications, please check my bibliography URL:

NCBI

 

Last Updated: 9/29/17