, 1991). From a cell biological perspective, the organization of dendrodendritic synapses raises the question of how specialized vesicle release and postsynaptic subdomains are established and maintained in close

proximity to each other in the same cell. Many fundamental questions regarding the formation and maintenance of these synapses remain unanswered (Figure 2). At presynaptic terminals, endocytosis is required for regenerating synaptic vesicles (Heuser and Reese, 1973 and Robitaille and Tremblay, 1987). Is there a similar specialization near dendrodendritic active zones? In hippocampal neurons, an endocytic zone adjacent to the PSD is required for retaining and recycling glutamate receptors at individual synapses, disruption of which results in a loss of synaptic glutamate receptors (Blanpied and Ehlers, 2004, Blanpied et al., 2002, Lu et al., 2007, Petrini et al., 2009 and Rácz et al., 2004). Perhaps a similar endocytic domain is Selleckchem Osimertinib responsible for maintaining neurotransmitter receptors or regenerating dendritic vesicles at dendrodendritic synapses. If this is the case, how is segregation maintained between the recycling membrane pools containing neurotransmitter and the recycling membrane pools containing receptors? If the axon terminal and dendritic release machinery

are the same, how do mitral Smad2 phosphorylation cells subvert the normal polarized trafficking itinerary of axonal molecules required for neurotransmitter release and redirect them to dendrites? Are there components that bridge postsynaptic densities and vesicle release sites that are required to maintain these subdomains in close but nonoverlapping proximity? What are the cell adhesion molecules that bridge the dendrodendritic synapse? The dendrodendritic synapse represents a remarkable exception to the normal

rules of neuronal cell polarity; thus the answers to these questions will provide insight not only into the details of olfactory circuitry, but also general principles of how cellular subdomains are specified and maintained. Dopamine has been observed in a variety of dendritic organelles including large dense core vesicles, small synaptic vesicles, and tubulovesicular structures resembling smooth ER in dopaminergic neurons (Björklund and Lindvall, 1975 and Nirenberg et al., 1996). Depletion of dendritic dopamine by reserpine treatment, a vesicular monamine not transporter (VMAT) inhibitor, was the first evidence that dopamine in dendrites was a secreted, biologically active pool of neurotransmitter (Björklund and Lindvall, 1975 and Nirenberg et al., 1996). Perhaps the best characterized neurons that exhibit dendritic dopamine release are dopamine neurons of the substantia nigra (SN), which have long striatal axonal projections. The anatomical separation of dendrites and axon terminals in the nigrostriatal circuit makes it possible to measure dendritic dopamine release with little contamination from axonal release.