Staining for the canonical axonal Ca2+ sensors synaptotagmin 1 and 2 revealed little Pazopanib supplier signal

in the somatodendritic compartment of SN dopamine neurons (Witkovsky et al., 2009). Staining for other typical axonal release molecules, including syntaxin1a/b, VAMP1, and synaptophysin, is also weak, suggesting a distinct ensemble of dendritic release factors. Indeed, VAMP2, SNAP25, and the plasma membrane t-SNARE syntaxin 3 are present throughout the somatodendritic compartment (Fortin et al., 2006 and Witkovsky et al., 2009). However, the only functional evidence that any of these proteins are involved in dendritic dopamine release comes from experiments demonstrating sensitivity to botulinum toxin A, which cleaves SNAP-25 (Fortin et al., 2006). In addition to being a mechanism for release of neurotransmitters, peptides, or other soluble factors, secretory granule fusion may serve as a mechanism for regulated delivery of specific transmembrane proteins to the dendritic plasma membrane. For example in axons, opioid receptors are localized to LDCVs containing

neuropeptides and are coinserted into the plasma membrane upon peptide release by LDCV fusion (Bao et al., 2003). Further studies will be required to determine whether coinsertion/secretion also serves as a mechanism for dendritic trafficking of membrane proteins. selleck chemical Neuroactive peptides and peptide hormones are also released from dendrites. Dendritic vasopressin and oxytocin release from magnocellular neurons of the supraoptic nucleus have been studied intensely as this system offers a unique anatomical arrangement allowing independent measure of axonal and dendritic peptide release. These neurons span the blood brain ever barrier with their dendrites situated in and receiving input from the CNS, and their axons projecting into the peripheral hypophyseal portal circulation. Thus, axonal exocytosis from these neurons results in peripheral release of neuropeptide,

which, in the case of oxytocin, mediates reproductive physiology including milk ejection and uterine contractions while dendritically released oxytocin remains in the CNS where it can modify various social behaviors. At the ultrastructural level, the dendrites of these neurons are filled with large dense core vesicles (LDCVs), which are often in close association with the plasma membrane (Figure 1D). Pow and Morris (1989) directly observed LDCV fusion intermediate “omega structures” in these cells over 20 years ago. As with other forms of regulated dendritic exocytosis, fusion of LDCVs is regulated by Ca2+, although the mechanisms of Ca2+ entry are not firmly established. Interestingly, NMDA receptor activation alone in the absence of cell firing appears to be sufficient to drive somatodendritic release of oxytocin from dorsomedial supraoptic nucleus neurons (de Kock et al., 2004).