From synapse to behavior: rapid modulation of defined neuronal types with engineered GABA(A) receptors. Export

@article{citeulike:1401953, abstract = {In mammals, identifying the contribution of specific neurons or networks to behavior is a key challenge. Here we describe an approach that facilitates this process by enabling the rapid modulation of synaptic inhibition in defined cell populations. Binding of zolpidem, a systemically active allosteric modulator that enhances the function of the GABA(A) receptor, requires a phenylalanine residue (Phe77) in the gamma2 subunit. Mice in which this residue is changed to isoleucine are insensitive to zolpidem. By Cre recombinase-induced swapping of the gamma2 subunit (that is, exchanging Ile77 for Phe77), zolpidem sensitivity can be restored to GABA(A) receptors in chosen cell types. We demonstrate the power of this method in the cerebellum, where zolpidem rapidly induces significant motor deficits when Purkinje cells are made uniquely sensitive to its action. This combined molecular and pharmacological technique has demonstrable advantages over targeted cell ablation and will be invaluable for investigating many neuronal circuits.}, address = {[1] Department of Clinical Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. [2] Present address: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. [3] These authors contributed equally to this work.}, author = {Wulff, Peer and Goetz, Thomas and Lepp\"{a}, Elli and Linden, Anni-Maija M. and Renzi, Massimiliano and Swinny, Jerome D D. and Vekovischeva, Olga Y Y. and Sieghart, Werner and Somogyi, Peter and Korpi, Esa R R. and Farrant, Mark and Wisden, William}, citeulike-article-id = {1401953}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nn1927}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nn1927}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17572671}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17572671}, day = {17}, doi = {10.1038/nn1927}, issn = {1097-6256}, journal = {Nat Neurosci}, keywords = {circuit\_busting, cre-lox, gaba}, month = {June}, posted-at = {2007-11-03 12:26:16}, priority = {0}, title = {From synapse to behavior: rapid modulation of defined neuronal types with engineered GABA(A) receptors.}, url = {http://dx.doi.org/10.1038/nn1927}, year = {2007} }

TY - JOUR ID - citeulike:1401953 L3 - citeulike-article-id:1401953 N2 - In mammals, identifying the contribution of specific neurons or networks to behavior is a key challenge. Here we describe an approach that facilitates this process by enabling the rapid modulation of synaptic inhibition in defined cell populations. Binding of zolpidem, a systemically active allosteric modulator that enhances the function of the GABA(A) receptor, requires a phenylalanine residue (Phe77) in the gamma2 subunit. Mice in which this residue is changed to isoleucine are insensitive to zolpidem. By Cre recombinase-induced swapping of the gamma2 subunit (that is, exchanging Ile77 for Phe77), zolpidem sensitivity can be restored to GABA(A) receptors in chosen cell types. We demonstrate the power of this method in the cerebellum, where zolpidem rapidly induces significant motor deficits when Purkinje cells are made uniquely sensitive to its action. This combined molecular and pharmacological technique has demonstrable advantages over targeted cell ablation and will be invaluable for investigating many neuronal circuits. JF - Nat Neurosci SN - 1097-6256 AD - [1] Department of Clinical Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. [2] Present address: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. [3] These authors contributed equally to this work. TI - From synapse to behavior: rapid modulation of defined neuronal types with engineered GABA(A) receptors. KW - circuit_busting KW - cre-lox KW - gaba AU - Wulff, Peer AU - Goetz, Thomas AU - Leppä, Elli AU - Linden, Anni-Maija AU - Renzi, Massimiliano AU - Swinny, Jerome D AU - Vekovischeva, Olga Y AU - Sieghart, Werner AU - Somogyi, Peter AU - Korpi, Esa R AU - Farrant, Mark AU - Wisden, William PY - 2007/06/17/ UR - http://dx.doi.org/10.1038/nn1927 ER -