In some cases, such a positive feedback loop implements a bistable switch to ensure that once a behavioral sequence is initiated, Screening Library it proceeds inexorably to

its conclusion, such as in the EH/ETH positive feedback loop controlling insect ecdysis (Figure 4A). In other cases, feedback loops modulate sensory inputs, such as in the worm sensory feedback loop wherein a peptide secreted by a sensory neuron acts in an interneuron that, in turn, secretes a peptide that acts on the sensory neuron (Figure 4B). Increasingly sophisticated genetic methods promise the availability of tools (genetic toolkits) to systematically categorize neuropeptide and neuropeptide receptor content for individual

cell types. It is now possible to assay the functional contributions of such modulatory signaling: the contributions of single peptides in cells that secrete multiple peptides versus the aggregate signaling from that cell type. This is particularly important in C. elegans, in which the entire nervous system contains only ∼300 neurons, but expressed over BI 2536 cell line 100 distinct neuropeptides. Such technical facility will increase even more the value of genetic model organisms flies and worms for studies of the neural basis of behavior. It is important to recognize that C. elegans and Drosophila melanogaster are highly derived species whose genomic signatures and behavioral profiles are highly specific to their evolutionary history. They offer views of genetic machinery and behavioral repertoires that must be interpreted in light of species-specific evolution, thereby enabling the application of lessons learned in invertebrates to mammals. This brings us to our final point—that the regulation of behavior by neuropeptides in invertebrates relies on three types of studies—but only two of these are currently given the attention they deserve. The first type involves genetics,

genomics, and endocrinology. GPX6 What are neuropeptide sequences, and which are their receptors? Where are these proteins expressed and how do they signal? How unique or redundant are their actions? The second type involves neurophysiology, functional imaging, and neuroanatomy. When are neuropeptide signals sent and how quickly do they act? At what system levels do they work? What is their relation to sensory inputs, to CPGs, and to motor outputs? The third type is behavioral biology. What are the details of animal behavior that are modulated by neuropeptides and what are the behavioral consequences of such modulation. Almost all current behavioral paradigms rely on placing animals in intentionally impoverished environments so as to isolate a specific feature of a single behavior for experimental isolation and manipulation.