User:Katie S. Kindt

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Katie S. Kindt

I am currently a postdoctoral fellow in the Nicolson lab at Oregon Health and Sciences University.

Education

  • 2007-2013, Postdoctoral fellow, Oregon Hearing Research Center/ Vollum Institute

In the lab of Teresa Nicolson

  • 2006-2007 Postdoctoral fellow, MRC Cambridge

In the lab of William Schafer

  • 2000-2006, PhD, University of CA - San Diego

In the lab of William Schafer

  • 2000, BS, University of WI - Eau Claire

In the lab of Scott Hartsel

Current research interests

Scanning electron micrograph of the apical surface of a zebrafish neuromast
Live image of zebrafish hair cells expressing tagged Ribeye protein


Summary: As a postdoc in the lab of Teresa Nicolson I have applied my in vivo imaging expertise to study hearing in the vertebrate Danio rerio. I have created transgenic zebrafish expressing a cytoplasmically localized GECI specifically in hair cells, to study the onset and development of mechanosensation. Currently I am pushing my system farther to image and study activity in neuronal microcompartments, such as the presynaptic bouton and postsynaptic density. Although critical for understanding the complex function and development of neurons, this type of resolution is lacking from traditional electrophysiological approaches. Therefore my current and future research programs utilize transgenic zebrafish that express subcelluarly localized GECIs within the neurons of the zebrafish auditory escape response circuit. Such tools are not available for studying auditory and vestibular function in mammals, and therefore my research is uniquely poised to address important scientific questions in hair cell sensory neuroscience.


  • Mechanosensitive cilia in Zebrafish hair cells


Hair cells are mechanosensory receptors that utilize apical hair bundles to sense sound and movement. Each hair bundle is comprised of a single primary cilium (kinocilium) flanking multiple rows of stereocilia. Tip links interconnect stereocilia and are thought to gate mechanotransduction channels. In cochlear hair cells, kinocilia regress shortly after birth and physical removal of kinocilia from vestibular hair cells does not affect mechanotransduction. Therefore, the function of kinocilia in mechanotransduction in mature hair cells is not evident. By applying in vivo imaging of activity and structure sequentially with scanning electron microscopy, we have uncovered a novel role for kinocilia in mechanosensation during development. Nascent hair cells require kinocilia and kinocilial links for mechanosensitivity. Although nascent cells have correct planar polarity, functional polarity is reversed. Later in development, a switch to correctly polarized mechanosensitivity coincides with the formation of tip links and the onset of tip link-dependent mechanotransduction.


  • Calcium imaging at the hair cell ribbon synapse

Hair cells, photoreceptors and bipolar cells have a specialized presynaptic density, also known as the synaptic ribbon. The synaptic ribbon is an electron dense structure that acts as a scaffold to tether vesicles adjacent to the presynaptic membrane near Ca2+ channels (CaV1.3). At synaptic ribbons exocytosis is coupled to graded changes in membrane potential rather than an action potential. This graded response is critical; it enables synaptic ribbons to encode the frequency, intensity and phase of stimuli. Currently I am studying the structural differences that impart unique functional attributes in mature and developing synaptic ribbons, a fundamental question relevant for specifically understanding hair-cell function and broadly for understanding all synapses.


Thesis work: Dopaminergic modulation of the C. elegans mechanosensory system

GFP expression in C. elegans touch receptor neurons

Summary:

Dopamine has been implicated in the modulation of diverse forms of behavioral plasticity, including appetitive learning and addiction. An important challenge is to understand how dopamine’s effects at the cellular level alter the properties of neural circuits to modify behavior. In the nematode C. elegans, dopamine modulates habituation of an escape reflex triggered by body touch. In the absence of food, animals habituate more rapidly than in the presence of food; this contextual information about food availability is provided by dopaminergic mechanosensory neurons that sense the presence of bacteria. We find that dopamine alters habituation kinetics by selectively modulating the touch responses of the anterior-body mechanoreceptors; this modulation involves a D1- like dopamine receptor, a Gq/PLC-b signaling pathway, and calcium release within the touch neurons. Interestingly, the body touch mechanoreceptors can themselves excite the dopamine neurons, forming a positive feedback loop capable of integrating context and experience to modulate mechanosensory attention.



Publications

Clemens Grisham R, Kindt KS, Finger-Baier K, Schmid B, Nicolson T.Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells. PLoS One. 2013 Apr 12;8(4):e60866. PubMed PMID: 23593334 [1].

Sheets L, Kindt KS, Nicolson T. Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells. J Neurosci. 2012 Nov 28;32(48):17273-86. PubMed PMID: 23197719 [2].

Kindt KS, Finch G, Nicolson T. Kinocilia mediate mechanosensitivity in developing zebrafish hair cells. Dev Cell. 2012 Aug 14;23(2):329-41. PubMed PMID: 22898777 [3].

Chatzigeorgiou M, Grundy L, Kindt KS, Lee WH, Driscoll M, Schafer WR. Spatial asymmetry in the mechanosensory phenotypes of the C. elegans DEG/ENaC gene mec-10. J Neurophysiol. 2010 Dec;104(6):3334-44. Epub 2010 Sep 29. PubMed PMID: 20881202 [4].

Chatzigeorgiou M, Yoo S, Watson JD, Lee WH, Spencer WC, Kindt KS, Hwang SW, Miller DM 3rd, Treinin M, Driscoll M, Schafer WR. Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors. Nat Neurosci. 2010 Jul;13(7):861-8. Epub 2010 May 30. PubMed PMID: 20512132 [5].

Kindt KS, Quast KB, Giles AC, De S, Hendrey D, Nicastro I, Rankin CH, Schafer WR. Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans. Neuron. 2007 Aug 16;55(4):662-76. PubMed PMID: 17698017 [6].

Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR. Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat Neurosci. 2007 May;10(5):568-77. Epub 2007 Apr 22. PubMed PMID: 17450139 [7].

Froekjaer-Jensen C, Kindt KS, Kerr RA, Suzuki H, Melnik-Martinez K, Gerstbreih B, Driscol M, Schafer WR. Effects of voltage-gated calcium channel subunit genes on calcium influx in cultured C. elegans mechanosensory neurons. J Neurobiol. 2006 Sep 1;66(10):1125-39. PubMed PMID: 16838374 [8].

Sanyal S, Wintle RF, Kindt KS, Nuttley WM, Arvan R, Fitzmaurice P, Bigras E, Merz DC, Hebert TE, van der Kooy D, Schafer WR, Culotti JG, Van Tol HH. Dopamine modulates the plasticity of mechanosensory responses in Caenorhabditis elegans. EMBO J. 2004 Jan 28;23(2):473-82. Epub 2004 Jan 22. PubMed PMID: 14739932 [9].

Kindt KS, Tam T, Whiteman S, Schafer WR. Serotonin promotes G(o)-dependent neuronal migration in Caenorhabditis elegans. Curr Biol. 2002 Oct 15;12(20):1738-47. PubMed PMID: 12401168 [10].

Baas B, Kindt K, Scott A, Scott J, Mikulecky P, Hartsel SC. Activity and kinetics of dissociation and transfer of amphotericin B from a novel delivery form. AAPS PharmSci. 1999;1(3):E10. PubMed PMID: 11741206[11].

Hartsel SC, Baas B, Bauer E, Foree LT Jr, Kindt K, Preis H, Scott A, Kwong EH, Ramaswamy M, Wasan KM. Heat-induced superaggregation of amphotericin B modifies its interaction with serum proteins and lipoproteins and stimulation of TNF-alpha. J Pharm Sci. 2001 Feb;90(2):124-33. PubMed PMID: 11169529 [12].

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