AgRP/NPY neurons also project to the paraventricular nucleus; selleck kinase inhibitor in a complex series of experiments based in part on selective optogenetic activation and inactivation, AgRP/NPY axonal projections to oxytocin neurons were found to be critical for stimulation of feeding elicited from activation of AgRP/NPY cells. Both NPY and GABA inhibition of paraventricular oxytocin cells contributed to the initiation of feeding (Atasoy et al., 2012); the role of the GABA projection from the AgRP/NPY neuron to the PBN was interpreted in the context of visceral malaise. Another independent line of work has shown that knocking out glutamate neurotransmission from SF1 neurons of the hypothalamic

ventromedial nucleus disturbs glucose

regulation and causes mice to suffer from hypoglycemia during fasting and to have defective responses to insulin-induced hypoglycemia (Tong et al., 2007). One substantial mechanism underlying neuropeptide modification of neuronal activity is the modulation of neurotransmitter release by direct peptide actions on the axon terminal (Miller, 1998; Willis, 2006). Some peptides, for instance NPY (Colmers et al., 1988), somatostatin (López-Huerta et al., 2012; Tallent and Siggins, 1997), and dynorphin, tend to reduce transmitter release, whereas others such as hypocretin (van den Pol et al., 1998) or glucagon-like peptide 1 (Acuna-Goycolea and van den Pol, 2004) enhance release probability. Neuropeptide receptors are found Navitoclax molecular weight on both glutamate and GABA axon terminals (Figure 6). In some regions of the brain, presynaptic modulation has been suggested crotamiton as the primary or only role of some neuropeptides. NPY, for instance, acts to a large degree by inhibiting neurotransmitter release from

excitatory CA3 neurons in the hippocampus; NPY had no detectable effect on either the active or passive membrane properties of CA3 pyramidal neuron cell bodies but reduced release of glutamate from axons of these cells that terminated on CA1 pyramidal cells by a mechanism based on reduction of calcium influx into the axon terminal (Colmers et al., 1988). In the dentate gyrus, NPY Y2 receptors expressed on axon terminals inhibited glutamate or GABA release, and NPY Y1 receptors on granule cells mediated a cellular inhibition (Sperk et al., 2007). Insight into a potential function of hippocampal NPY is provided by NPY gene knockout (KO) mice which maintained normal electrophysiological activity in the hippocampus but showed poor recovery after induction of limbic seizures with the glutamate agonist kainate, which caused death in the majority of NPY-KO mice compared with little death in normal mice treated with similar doses of kainate (Baraban et al., 1997). Similarly, NPY Y5-receptor KO mice were also more sensitive to kainate-induced seizures (Marsh et al., 1999a).