Development and plasticity of inhibitory circuits.
Dr. Kandler's laboratory investigates the development and plasticity of synaptic circuits in the central auditory system. How do developing auditory circuits become functionally and structurally fine-tuned to their task? What role does neuronal activity or early hearing experience play in these processes? What are the mechanisms by which experience or certain activity patterns are transformed into optimized synaptic circuits? How do mature circuits adapt to hearing loss and why does hearing loss sometimes lead to the experience of phantom sounds (tinnitus)?
To address these questions, we are using a variety of physiological, imaging, anatomical, and behavioral approaches, including laser scanning photostimulation with caged glutamate to map functional connectivity of networks, 2-photon calcium imaging to characterize postsynaptic responses, ontogenetic to activate defined synaptic inputs, quantitative single cell reconstructions to investigate structural plasticity, and acoustic startle responses to test auditory processing on a behavioral level. We apply these techniques to normal or genetically modified mice and mice with defined healing loss and/or tinnitus.
Trainees in Dr. Kandler's laboratory have the opportunity to engage in a variety of research projects addressing the mentioned above questions.
Sturm, J., Nguyen, T.D. and Kandler, K. Development of intrinsic connectivity in the central nucleus of the mouse inferior colliculus. J. Neuroscience, 34: 15032-46, 2014.
Clause, A., Kim, G., Sonntag, M., Weisz, C.J.C., Vetter, D.E., Rubsamen, D. and Kandler, K. The precise temporal pattern of pre-hearing spontaneous activity is necessary for tonotopic map refinement. Neuron, 82:822-35, 2014.
Nguyen, T.D., Wirblich, C., Aizenman, E., Schnell, M.J., Strick, P.L. and Kandler, K. Targeted single-neuron infection with rabies virus for transneuronal multisynaptic tracing. J Neurosci Methods. 2012 Jun 26;209(2): 367-370, 2012.
Kim, G. and Kandler, K. Paired recordings from distant inhibitory neuron pairs by a sequential scanning approach. J Neurosci Methods. 200: 185-189, 2011.
Castro, J.B. and Kandler, K. Changing tune in auditory cortex. Nat Neurosci. 13: 271-273, 2010.
Noh, J., Seal, R.P., Garver, J.A., Edwards, R.H. and Kandler, K. Glutamate co-release at GABA/glycinergic synapses is crucial for the refinement of an inhibitory map. Nature Neuroscience 13: 232-328, 2010.
Kandler, K., Clause, A. and Noh, J. Tonotopic reorganization of developing auditory brainstem circuits. Nat Neurosci. 12: 711-717, 2009.
Hershfinkel, M., Kandler, K., Knoch, M.E., Dagan-Rabin, M., Aras, M.A., Abramovitch-Dahan, C., Sekler, I. and Aizenman, E. Intracellular zinc inhibits KCC2 transporter activity. Nat Neurosci. 12: 725-727, 2009.
Seal RP, Akil O, Yi E, Weber CM, Grant L, Yoo J, Clause A, Kandler K, Noebels JL, Glowatzki E, Lustig LR, Edwards RH. (2008) Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 57:263-75.
Gillespie, D.C., Kim, G. and Kandler, K. Inhibitory synapses in the developing auditory system are glutamatergic. Nature Neuroscience, 8: 332-338, 2005.