There is now strong evidence that dysfunction of receptor- and/or ion channel-mediated synaptic transmission underlies a number of disorders in the central and peripheral nervous system. One major piece of evidence comes directly from transgenic mice. For instance, deletion of GABAB receptors has been correlated with epilepsy, cognitive impartment, sensorimotor abnormalities or anxiety and depression alterations; deletion of GIRK subunits has been correlated with increased seizure propensity, hyperalgesia, blunted analgesia and hyperactivity; or deletion of Cav channels has been correlated with absence seizures, ataxia, nociception, anxiety, impaired spatial memory and altered response to cocaine. The laboratory uses a multidisciplinary effort aimed at defining the changes in the coupling, cellular and subcellular localization of receptors, effector ion channels and related signaling molecules, thus allowing us to identify mechanisms generating a given pathology, as well as the mechanism of action of drugs.

Related publications

Hearing M, Kotecki L, Marron Fernandez de Velasco E, Fajardo-Serrano A, Chung HJ, Luján R, Wickman K. (2013) Repeated Cocaine Weakens GABAB-Girk Signaling in Layer 5/6 Pyramidal Neurons in the Prelimbic Cortex. Neuron 80(1):159-70.

Padgett C.L., Lalive A.L., Tan K.R., Terunuma M., Moss S.J., Martínez-Hernández J., Watanabe M., Luján R., Lüscher C. and Slesinger P.A. (2012) Methamphetamine-evoked depression of GABAB receptor signalling in GABA neurons of the VTA. Neuron 73(5):978-89.

Arora D, Hearing M, Haluk DM, Mirkovic K, Fajardo-Serrano A, Wessendorf MW, Watanabe M, Luján R, Wickman K. (2011) Acute cocaine exposure weakens GABA(B) receptor-dependent G-protein-gated inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental area. Journal of Neuroscience 31(34):12251-7.

Allen D, Nakayama S, Kuroiwa M, Nakano T, Palmateer J, Kosaka Y, Ballesteros C, Watanabe M, Bond CT, Luján R, Maylie J, Adelman JP, Herson PS. (2011) SK2 channels are neuroprotective for ischemia-induced neuronal cell death. J Cereb Blood Flow Metab 31(12):2302-12.

Brown MT, Bellone C, Mameli M, Labouèbe G, Bocklisch C, Balland B, Dahan L, Luján R, Deisseroth K, Lüscher C (2010) Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation. PLoS One 5(12):e15870.

Nassirpour R, Bahima L, Lalive AL, Lüscher C, Luján R, Slesinger PA. (2010) Morphine- and CaMKII-dependent enhancement of GIRK channel signalling in hippocampal neurons. Journal of Neuroscience 30(40):13419-30.

Arora D, Haluk DM, Kourrich S, Pravetoni M, Fernández-Alacid L, Nicolau JC, Luján R, Wickman K. (2010) Altered neurotransmission in the mesolimbic reward system of Girk mice. Journal of Neurochemistry 114(5):1487-97.