Cell Calcium. not dopaminergic. Outer retinal varicosities of this putative GABAergic IPC did AKT1 colocalize synaptic vesicle protein 2a, suggesting they possessed a conventional vesicular release mechanism. retina, glycine colocalizes with somatostatin (Smiley and Basinger, 1988) and in cat and mouse retinal IPCs GABA colocalizes with dopamine (W?ssle and Chun, 1988; Contini and Raviola, 2003). The main goals of the present study are to describe the anatomical business of dopaminergic interplexiform (DA-IPC) processes in the outer layers of rodent (mouse and rat) retinas, and to probe whether those processes have the appropriate presynaptic machinery for vesicle-dependent release of dopamine and/or GABA. The relevance of this question is that the mechanisms by which dopamine is usually released are still not fully understood and appear not to be homogeneous between somatodendritic and axonal compartments of the cell. For example, in dopaminergic neurons of the substantia nigra the release of dopamine by their axonal terminals in striatum shows a more marked dependence on intracellular calcium than does release from your somatodendritic compartment (Chen et al., 2006). In mammalian retinas, dopaminergic processes have a cluster of vesicles and paramembranous membrane density typically associated with chemical synapses (Kolb et al., 1990), whereas the somatic compartment, although known to release dopamine, lacks morphologically defined presynaptic zones (Puopolo et al., 2001). Moreover, the finding that the dopaminergic IPC also is GABAergic complicates the interpretation of anatomical data in that it is still not fully established whether the presynaptic specializations of DA processes are associated with dopamine, GABA, or both (Contini and Raviola, 2003). As a further complication, around the postsynaptic side retinal dopamine receptors typically are not located immediately adjacent to the presynaptic terminal. Instead, dopamine reaches its target cells by diffusion over distances of up to tens of microns (Witkovsky et al., 1993; Bjelke et al., 1996), which means that the characteristic close apposition of pre- and postsynaptic terminal specializations may represent the GABAergic component, but not the dopaminergic component, at synapses for which the dopaminergic neuron is the presynaptic element (Contini and Raviola, 2003). In spite of the absence of certain anatomical features associated with chemical synapses, there is substantial evidence that DA-IPCs (as well as DA amacrine cells) release dopamine by an exocytotic mechanism in the inner retina. Dopamine release, measured either from the whole retina or from individual DA perikarya, is usually calcium-dependent (Tamura et al., 1996; Puopolo et al., Laurocapram 2001). Immunocytochemical findings document the presence in DA presynaptic terminals and perikarya of the vesicular monoamine transporter type 2 (VMAT2; Puopolo et al., 2001; Witkovsky et al., 2005), which is the brain isoform responsible for transporting dopamine into synaptic vesicles or an comparative membrane-bound compartment (Peter et al., 1995). Additional presynaptic proteins associated with vesicle docking, priming, and fusion are present in the ringlike axon terminals (Witkovsky et al., Laurocapram 2005), as are Cav 2.2 calcium channels (Witkovsky et al., 2006; also called 1B or N type; cf. Catterall et al., 2003, for Ca channel nomenclature) which often are implicated in transmitter release. The obtaining by Puopolo et al. (2001) that dopamine release from perikarya occurs as a pulsatile event indicates fusion of a dopamine-containing vesicle or comparable membrane compartment, rather than by reverse transport. The evidence for dopamine release in the outer retina, on the other hand, is not well established. In some retinas, presynaptic terminals from DA-IPCs onto horizontal and bipolar cells are reported (Dowling and Ehinger, 1975; Frederick et al., 1982; Kolb et al., 1990). The possibility, however, that this DA-IPC also colocalized another neurotransmitter was not evaluated. That is, it has not been established that this presynaptic specializations are specifically related to the release Laurocapram of dopamine. Given the volume conduction of dopamine in the retina (Witkovsky et al., 1993), activity-related changes in extracellular dopamine concentration cannot be readily linked to specific release sites. The data of the present statement indicate that IPC distal processes can package dopamine into membrane-bound compartments that are not standard synaptic vesicles. In these distal processes, however, the voltage-gated calcium channels and several other presynaptic.