Their calculations suggest that a concentration of 260 pg/ml can selleck inhibitor be achieved in 1 min, which seems consistent with the concentrations of 1000 pg/ml that were measured by microdialysis from the SON (Neumann et al., 1993). This still leaves unclear how OT spreads after release, to where it diffuses, and how quickly and at what concentrations.

In the septal nuclei in the forebrain 4–5 mm away from the SON, OT concentrations are raised by stimuli to the SON, but to concentrations 10-fold lower than in the SON itself (Leng and Ludwig, 2008). Though such concentrations may be effective in eliciting responses by OT, it is also clear that delay times for obtaining effects will be considerable. Alternatively, it is possible that OT from the hypothalamus arrives at various brain regions by axonal release from OT containing fibers specifically targeting the brain areas expressing the oxytocin receptor (OTR). We recently explored this issue by infecting rat PVN, AN, and SON hypothalamic nuclei with a virus construct

Selleckchem GSK1210151A that assured fluorescent protein and blue light-sensitive Channelrhodopsin-2 expression under the promoter of OT. This revealed an extensive network of OT fibers in various areas of the brain, including the amygdala (Knobloch et al., 2012, see Table 1). It allowed moreover the induction of local OT release from axonal fibers by optical activation using blue light targeted to areas of interest with strong concentration of fibers. In this way, we could show that blue light exposure of the amygdala decreased fear responses to levels similar to those produced by external application of OT targeted to the amygdala through cannulae (Viviani et al., 2011). The effects were blocked by preapplication of OTR antagonists, thereby demonstrating the involvement of OTRs and with it, the effect

of endogenous OT release. Decreases in freezing followed as fast as 2 s and on average around 20 s Rutecarpine after onset of blue light (Knobloch et al., 2012). Such a short delay time makes it unlikely that these effects of endogenous OT in vivo are due to a diffusion of the nona-peptide from OTergic hypothalamic nuclei. Taken together, these findings imply an important role of nerve fiber-carried delivery of OT to targets distant from the hypothalamic OT-ergic nuclei. An interesting model has been proposed by Landgraf and Neumann (2004) in which they suggest that axonal release of neuropeptides in limbic area could provide a local precise spatiotemporal, point-to-point regulation of the basal level of neuropeptides, in addition to delivery by continuous diffusion. Neuropeptides could communicate with neurons and modulate different brain structures in a multimodal manner, both through a “wired,” axonal, fast, and focal manner as well as in an “unwired,” diffusive, slow, and global fashion.