, 2005, Miller and Katz, 2013, Usher and McClelland, 2001 and Wong and Wang,
2006) along with a variety of extensions that overcome sensitivity to mistuning (Cain VEGFR inhibitor et al., 2013, Goldman et al., 2003 and Koulakov et al., 2002). These theories would support integration within the cortical module (e.g., LIP). In contrast, our favorite idea for integration would involve control signals that effectively switch the LIP circuit between modes that either defend the current firing rate (i.e., stable persistent activity) or allow the rate to be perturbed by external input such as evidence from the visual cortex. A similar idea has been put forth by Schall and colleagues (Purcell et al., 2010). This is part of the larger idea mentioned in the section on Ferroptosis inhibitor drugs decisions about relevance. The result of this decision is a change in configuration of the LIP circuit such that the new piece of evidence can perturb the DV. To begin to address the circuit-level analyses of integration we need better techniques that can be used in primates and we need better testing paradigms in rodents. There is great promise in both of these areas and emerging enthusiasm for interaction
between these traditionally separate cultures. We need to control elements of the microcircuit in primates with optogenetics and DREADD (designer receptors exclusively activated by designer drugs, Rogan and Roth, 2011) technologies, and we need to identify relevant physiological properties of cortical circuits in more tractable animals (e.g., the mouse) that can be studied in detail. Ideally, the variety, reliability, and safety of viral expression systems will support such work in highly trained monkeys (e.g., Diester et al., 2011, Han et al., 2009 and Jazayeri et al., 2012), and the behavioral paradigms in mice will achieve the sensitivity to serve as assays for subtle manipulations of the circuit. Recall that the of most compelling microstimulation studies in the field of perceptual decision making (e.g., Salzman
et al., 1990) would have failed had the task included only easy conditions! Promising work from several labs supports the possibility of achieving this in rats (e.g., Brunton et al., 2013, Lima et al., 2009, Raposo et al., 2012, Rinberg et al., 2006 and Znamenskiy and Zador, 2013), and mice cannot be far behind (Carandini and Churchland, 2013). Indeed, it now appears possible to study persistent activity in behaving mice (Harvey et al., 2012). These are early days, but we are hopeful that the molecular tools available in the mouse will yield answers to fundamental questions about integration and eventually to some of the other “principles” listed in Box 3. Many of the most important questions concern interactions between circuits.
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