Neuromodulation of circuit function has been studied for more than 40 years in crustaceans and mollusks. The crustacean stomatogastric ganglion (STG) contains ∼30 neurons and the crustacean cardiac ganglion

contains only nine neurons. Both are central pattern generating circuits that generate fictive motor patterns when removed from the animal, and both are modulated by a large number of different substances (Blitz and Nusbaum, 2011; Cruz-Bermúdez and Marder, 2007; Johnson et al., 2011; Marder and Bucher, 2007; Stein, 2009; Wiwatpanit et al., 2012). Figure 2 summarizes a partial list of what is known about the neuromodulatory control of the crab STG. These data were accumulated over the years by many laboratories using a combination of immunocytochemistry and biochemical techniques. Most recently, mass spectrometry has allowed buy VX-770 the identification and characterization of many individual members of a number of different peptide families (Dickinson et al., 2009; Ma et al., 2009a, 2009b, 2009c; Stemmler et al., 2010). Many of the same substances are released both by descending modulatory neurons and by neurosecretory structures

as hormones. It is unlikely that the STG is unusual in the number of its modulatory inputs. A large number of neuromodulators are known to have important functions in the Aplysia feeding circuit ( Brezina and Weiss, 1997; Furukawa et al., 2003; Koh and Weiss, 2007; Li et al., 2001; Proekt et al., 2005; Sweedler et al., 2002; Vilim et al., 2010; Wu et al., 2010), another system in which the search for modulators selleckchem has been intense. And certainly, the number of important peptide modulators known in C. elegans and Drosophila is also large ( Bargmann, 2012; Taghert and Nitabach, 2012). In contrast, there are relatively few vertebrate circuits, in which there have been determined attempts

to find all of the modulatory inputs to the circuit. But, whether there are five or 12 or 25 modulators that can influence the output of a given circuit in the brain, no circuit is likely to be modulated by only one or two substances, no matter how tempting it is to think that a single substance is solely responsible for through controlling a significant piece of the brain. The exogenous application of neuromodulatory substances and the stimulation of modulatory projection neurons can significantly alter circuit output (Blitz et al., 2004, 1999, 1995, 2008; Dando and Selverston, 1972; Dickinson et al., 2001; Dickinson and Marder, 1989; Dickinson et al., 1990; Dickinson and Nagy, 1983; Eisen and Marder, 1984; Flamm and Harris-Warrick, 1986a, 1986b; Hooper and Marder, 1984, 1987; Nagy and Dickinson, 1983; Nagy et al., 1988; Nusbaum and Marder, 1988, 1989a, 1989b; Saideman et al., 2006, 2007).