Glutamate acts as a neurotransmitter at most excitatory synapses and is involved in long-lasting plastic phenomena as well as in neuronal dead-associated pathology such as neurodegeneration. Our group characterized and identified functions for one of the glutamate receptors largely elusive to researchers, the kainate receptor. Two fundamental findings paved the way to this extent. Once the existence of these receptors in central neurons was demonstrated, the identification of a selective antagonist made possible their pharmacological isolation. As a result, we and others have found that the function of kainate receptors is double. They may work presynaptically to modulate transmitter release and postsynaptically, mediating part of the synaptic transmission at certain central synapses. Therefore, the general objective of our current project is to get further insight into the knowledge of these two functions in the brain. Moreover, although these receptors are ion channels, some of their modulatory capabilities involve triggering of a cascade of second messengers, implicating the existence of a non-canonical signalling pathway. We seek to identify the elements involved in such a pathway as well as to define their functional role in several aspects of the brain physiology. To this extent we are currently trying to identify proteins interacting with kainate receptors subunits by using a proteomic approach. The role of these proteins are investigated by performing biochemical, electrophysiological and confocal Ca2+ imaging experiments in brain slices and cultured neurons from normal and KO mice.

Selak S, Paternain AV, Aller IM, Picó E, Rivera R, Lerma J. (2009) A role for SNAP25 in internalization of kainate receptors and synaptic plasticity. Neuron  63, 357-71.

Rivera R, Rozas JL and Lerma J  (2007) PKC-dependent Autoregulation of Membrane Kainate Receptors. EMBO Journal, 26, 4359-67

Lerma J. (2006) Kainate Receptor Physiology, Curr. Op. Pharmacol. 6, 89-97.

Christensen, JK, Paternain, AV, Selak, S, Ahring PK and Lerma, J. (2004) A mosaic of functional kainate receptors in hippocampal interneurons. J Neuroscience 24, 8986-93.

Paternain, A.V., Cohen, A., Stern-Bach, Y. and Lerma, J. (2003) A role for extracellular Na⁺ in the channel gating of native and recombinant kainate receptors. J Neuroscience 23, 8641-8648.

Rozas, J.L., Paternain A.V. and Lerma J. (2003) Non-canonical signaling by ionotropic kainate receptors. Neuron 39, 543–553

Lerma, J. (2003). Roles and rules of kainate receptors in synaptic transmission. Nature Rev Neurosci 4, 481-95.

Regalado, M. P., Villarroel, A. and Lerma, J. (2001) Inter-subunit cooperativity in the NMDA receptor. Neuron. 32, 1085-1096.

Lerma, J., Paternain, A.V., Rodríguez-Moreno, A., and López-García, J.C (2001) Molecular Physiology of Kainate Receptors. Physiologial Reviews. 81, 971-998

Rodríguez-Moreno, A., López-García, J.C. and Lerma, J. (2000) Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons. Proc. Natl. Acad. Sci USA. 97, 1293-1298.

Paternain, A.V., Herrera, M.T., Nieto, M.A. and Lerma, J. (2000) GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and co-assamble to form functional receptor channels. J. Neurosci. 20, 1966-205.