Such information will not only provide fundamental insights into how the AIS affects AP generation and information processing in neurons, but may also open new avenues for targeted therapies to treat neurological disorders. “
“Neuropeptides are expressed and secreted throughout the mammalian brain, typically in combination with a fast neurotransmitter such as glutamate or GABA (Hökfelt et al., 2000). Neuropeptides are packaged in vesicles and several are known to be released this website in an activity-dependent manner (Ludwig and Leng, 2006). Neuropeptide expression is often regulated by neuronal

activity and many neurons are classified by their selective expression of different neuropeptides and neuropeptide receptors (Hökfelt et al., 2000). Such regulated and heterogeneous expression of neuropeptides suggests a precise function in neuron-to-neuron signaling. Indeed, many aspects of synapse and cell function are modulated XAV-939 concentration by neuropeptide-dependent activation of G protein-coupled receptors (GPCRs) (Strand, 1999 and Tallent, 2008). At the behavioral level, neuropeptides have profound and complex neuromodulatory effects on brain function: they regulate social bonding (Insel, 2010), feeding (Morton et al., 2006), sleep (Adamantidis et al., 2010), aversion (Knoll and Carlezon, 2010),

and reward (Le Merrer et al., 2009). Studies into neuropeptide systems have been limited by a paucity of experimental tools. The conditions that trigger neuropeptide release from neurons are largely unknown and currently available Parvulin methods of activating neuropeptide receptors in brain tissue prevent quantitative studies of their function. Although small-molecule agonists for many neuropeptide receptors are available, many GPCRs exhibit functional selectivity such that they are incompletely or unnaturally activated by synthetic ligands (Urban et al., 2007). Furthermore, neuropeptides can bind and activate multiple receptor subtypes present on the same cell with similar affinities (Lupica et al., 1992 and Svoboda et al.,

1999). Thus, exogenous application of peptide ligands, rather than synthetic agonists, more accurately mimics endogenous peptidergic signaling. However, compared to traditional pharmacological agents, peptides are large, hydrophobic molecules and thus diffuse slowly within the brain. Direct peptide application in vivo and in brain slices by perfusion, pressure injection (Williams et al., 1982), or iontophoresis (Travagli et al., 1995) produces a slowly rising, prolonged, and spatially imprecise presentation of the peptide. These methods offer poor control over the concentration of peptide delivered, largely limiting quantitative analysis to the effects of saturating doses for consistency (Duggan and North, 1983).