Hence MB-MPs SKI-606 order normally block the expression of the memory at the level of MB neurons via specific DA inhibition. How does NPF fit into this feeding circuit? NPF is expressed in only a small set of neurons in the fly brain and stimulating

those specific neurons by genetic manipulation revealed they operate upstream of the MB-MP inhibitory neurons: NPF neurons transmit the hunger state to unmask appetitive memory. Importantly, that neuropeptide NPF action was localized to MB-MP neurons by knocking down NPF Receptor selectively in MB-MP neurons—such a manipulation lead to a loss of appetitive memory display. Thus, NPF provides critical modulation of appetitive feeding behavior in the fly by directly inhibiting dopaminergic MB-MP cells that has the effect of disinhibiting MB neurons and therefore permitting the propagation of appetitive memory information. The likelihood that appetitive behavior is triggered by the conditioned odorant is determined by the competition between inhibitory systems in the brain (Krashes et al., 2009).

In Aplysia, a central pattern generator produces two competing feeding motor programs—one supporting ingestion and the other supporting egestion. Neuropeptides operate in consummatory SP600125 cell line phases of feeding behaviors to promote a phase switching from the ingestive to egestive programs. How they produce this effect provides remarkable cellular detail to the mechanisms of peptide modulation. Two critical components in this CPG system are (1) the B20 interneuron, Adenosine which promotes the egestive rhythm, and (2) the B40 interneuron, which promotes the ingestive rhythm ( Jing and Weiss, 2001, 2002). This form of circuit organization ensures that it is the balance of B40 and B20 activity that determines whether feeding responses to food stimuli are ingestive, intermediate, or egestive. As the animal ate and became sated, the subsequent change in feeding behavior was not simply

an inhibition of ingestive responses, but instead a replacement of those responses with nonfunctional (intermediate) and/or egestive motor responses ( Jing et al., 2007). B40 and B20 do not inhibit each other directly—instead the switch from ingestive to egestive behaviors as satiety increases represents the selection by external modulation. The Aplysia ortholog of the NPY neuropeptide, aNPY, contributes to this important modulatory control by acting as a critical trigger for reconfiguration of the multifunctional CPG network ( Jing et al., 2007). aNPY released from gut afferents within the CNS acts on the B20 interneuron to promote the switch to egestion. Separate gut afferents activate the identified neuron B18. B18 in turn releases aNPY to act on B20 and help effect the switch from ingestive to egestive modes.