Studies in my laboratory aim to determine the role of ATP-mediated (purinergic) neurotransmission in the mammalian retina. The retina is an ideal model system to study purinergic transmission in the context of a central nervous system for the following reasons: 1) The retinal circuit architecture is well characterized and readily accessible to a variety of imaging techniques, 2) genetic tools to manipulate key components of this circuit in a cell-types specific manner are available, 3) responses of retinal neurons to their natural stimulus (light) can be elicited with great precision and measured using electrophysiological methods and, 4) One of the receptor families activated by extracellular ATP, P2X receptors, is widely expressed in the retina. Many questions remain about the cellular source of extracellular ATP, under what conditions it is ATP released and which pathways in the retina are influenced by P2X- mediated signaling. An additional goal of ours is to determine if purinergic signaling influences neuronal development and plays a role in retinal diseases. To answer these questions, we use a combination of imaging and electrophysiological techniques in retinas from wild type and genetically modified mice. We thus hope not only to reveal the role of purinergic signaling in the retina but also try to provide a framework for understanding the role of ATP-signaling in the mammalian brain.
- Nicke, A., Kuan, Y.H., Masin, M., Bender, O., Rettinger, J., Marquez-Klaka, B., Górecki, D.C., Murrell-Lagnado, R., and Soto, F. (2009) A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 KO mice. Journal of Biological Chemistry, 284:25813-25822.
- Kucenas, S., Soto, F., Cox, J.A. and Voigt, M.M. (2006) Selective labeling of central and peripheral sensory neurons in the developing zebrafish using P2X(3) receptor subunit transgenes. Neuroscience 138:641-652.
- Masin M., Kerschensteiner D., Dümke K., Rubio M.E., Soto F. (2006) Fe65 interacts with P2X2 subunits at excitatory synapses and modulates receptor function. Journal of Biological Chemistry 281:4100-4108.
- Nicke, A, Kerschensteiner, D. and Soto, F. (2005) Biochemical and functional characterization of the heteromeric receptor formed by P2X1 and P2X4 subunits. Journal of Neurochemistry, 92, 925-933.
- Ruppelt, A., Ma, W., Borchardt, K., Silberberg, S.D. and Soto, F. (2002) Genomic structure, developmental distribution and functional properties of the chicken P2X5 receptor. Journal of Neurochemistry, 77, 1256-1265.
- Rubio, M. E. and Soto, F. (2001) Distinct localization of P2X receptor at excitatory postsynaptic specializations. Journal of Neuroscience, 21, 641-653.