Development and plasticity of inhibitory circuits.
Research in Dr. Kandler's laboratory focuses on the question of how neuronal circuits are established and modified during brain development. Ongoing work uses the auditory brainstem as a model system to explore the cellular mechanisms by which neuronal activity regulates the reorganization of inhibitory connections and the precise functional alignment of excitatory-inhibitory networks. Techniques applied in the laboratory include whole-cell patch clamp recordings from visually identified neurons, confocal calcium imaging, focal photolysis of caged neurotransmitters (photostimulation), genetic manipulations of developing neurons using particle mediated gene transfer, intracellular dye injections, immunohistochemistry, and in vitro tracing of neuronal connections. These techniques are primarily applied to acute and cultured brain slices prepared from normal and genetically altered mice.
Students in Dr. Kandler's laboratory have the opportunity to engage in a variety of research projects, such as investigating the functional properties of early synaptic transmission and synaptic integration, characterizing developmental changes in functional connection patterns, deciphering intracellular pathways responsible for plasticity in inhibitory synapses, and examining the functional role of ion transporters and neurotransmitters which are transiently expressed during the period of synaptic refinement.
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.
Kullmann, P.H.M. and Kandler, K. Dendritic Ca2+ responses in neonatal LSO neurons elicited by glycinergic/GABAergic synapses and action potentials. Neuroscience, 12;154(1): 338-45, 2008.
Ene, A., Kalmbach, A. and Kandler, K. Metabotropic glutamate receptors in the lateral superior olive activate TRP-like channels: Age and experience-dependent regulation. J Neurophysiol. 97: 3365–3375, 2007.