, 2008, Freund and Buzsáki, 1996, Kawaguchi and Kondo, 2002, Kawaguchi and Kubota, 1998, Klausberger and Somogyi, 2008, Markram et al., 2004, Monyer and Markram, 2004, Mott and Dingledine, 2003, Somogyi and Klausberger, 2005 and Somogyi et al., 1998). We are thus facing a discrepancy between

the vast and detailed knowledge of inhibitory mechanisms and properties and our limited understanding of how these mechanisms and properties play together to contribute to cortical function. In other words, we now have more details about interneurons than we know BAY 73-4506 mw what to do with. A clear example of this discrepancy has been the spectacular and still ongoing characterization of the many types of cortical inhibitory interneurons on one hand and our very poor understanding of what each type contributes to cortical processing on the other hand. How will further efforts

bring us closer to understanding the role of inhibition in cortical function? New methodological approaches offer an unprecedented ability to precisely determine the functional properties of distinct inhibitory circuits. A variety of genetic tools are now available to perturb neuronal activity with exquisite spatial and temporal precision (Fenno et al., 2011, Kim et al., 2009, Magnus et al., 2011, Rogan and Roth, 2011 and Tan et al., 2006). However, a critical factor in using these genetic tools to dissect circuit function is the capacity to target them to particular types of neurons using cell-specific promoters. Thankfully, the abundance of studies characterizing biochemical and genetic phenotypes Decitabine manufacturer of cortical inhibitory neurons makes this possible. For example, these characterizations have established the foundations

for designing a variety of currently available mouse lines in which Cre recombinase can be used to target genetic tools to discrete subtypes of interneurons, such as parvalbumin-expressing basket cells or somatostatin-expressing Metalloexopeptidase Martinotti cells (Taniguchi et al., 2011). The ability to selectively target and perturb specific inhibitory circuits will lead to a better mechanistic understanding of their exact role in cortical function and help reveal the biological advantage of such a variety of inhibitory processes. Furthermore, identifying the specific roles of cortical inhibitory interneurons will help us understand their contribution to neurological or cognitive disorders. We look forward to a significant advance in our knowledge of how inhibition shapes cortical activity. We thank Dr. Matteo Carandini for helpful comments. Work in the authors’ labs supported by R01DC04682 (J.S.I.) and by NS069010, the Howard Hughes Medical Institute, and Gatsby Foundation (M.S.). ”
“Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are both devastating neurological diseases.