Extrasynaptic release of GABA and dopamine by retinal dopaminergic neurons

Abstract

One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. In the mouse retina, dopaminergic amacrine (DA) cells synthesize both dopamine and GABA. Both transmitters are released extrasynaptically and act on neighbouring and distant retinal neurons by volume transmission. In simultaneous recordings of dopamine and GABA release from isolated perikarya of DA cells, a proportion of the events of dopamine and GABA exocytosis were simultaneous, suggesting co-release. In addition, DA cells establish GABAergic synapses onto AII amacrine cells, the neurons that transfer rod bipolar signals to cone bipolars. GABA A but not dopamine receptors are clustered in the postsynaptic membrane. Therefore, dopamine, irrespective of its site of release-synaptic or extrasynaptic-exclusively acts by volume transmission. Dopamine is released upon illumination and sets the gain of retinal neurons for vision in bright light. The GABA released at DA cells' synapses probably prevents signals from the saturated rods from entering the cone pathway when the dark-adapted retina is exposed to bright illumination. The GABA released extrasynaptically by DA and other amacrine cells may set a 'GABAergic tone' in the inner plexiform layer and thus counteract the effects of a spillover of glutamate released at the bipolar cell synapses of adjacent OFF and ON strata, thus preserving segregation of signals between ON and OFF pathways.

High-resolution imaging of cellular dopamine efflux using a fluorescent nanosensor array

“…Hotspots have been discussed in the past but the lack of spatial resolution of electrode-based methods made it impossible to directly pinpoint release sites on single cells (42). It is also known that neurons do not necessarily form well-defined synapses and therefore it is not known a priori where cells release signaling molecules (43).…”

GABA‐like immunoreactivity in Biomphalaria: Colocalization with tyrosine hydroxylase‐like immunoreactivity in the feeding motor systems of panpulmonate snails

“…Increasing evidence supports the hypothesis that classical neurotransmitters can be colocalized in individual neurons (Borisovska & Westbrook, ; Gutíerrez, ; Seal & Edwards, ; Vaaga, Borisovska, & Westbrook, ). One such combination, γ–aminobutyric acid (GABA) with dopamine (DA), has been reported in several cell types within vertebrate nervous systems, including periglomerular cells of the mouse olfactory bulb (Borisovska, Bensen, Chong, & Westbrook, ; Liu, Plachez, Shao, Puche, & Shipley, ; Maher & Westbrook, ), retinal amacrine cells (Hirasawa, Contini, & Raviola, ; Hirasawa, Puopolo, & Raviola, ), mouse nigrostriatal and ventral tegmental cells (Tritsch, Ding, & Sabatini, ; Tritsch, Granger, & Sabatini, ; Trudeau et al, ), nerve terminals of the Xenopus laevis pituitary (de Rijk, van Strien, & Roubos, ), and neurons in the spinal cord of the sea lamprey (Barreiro‐Iglesias, Villar‐Cerviño, Anadón, & Rodicio, ). While proposed mechanisms of release from GABA‐DA neurons range from independent nonsynaptic volume transmission in the retina to co‐release from shared synaptic vesicles in the striatum, much remains unknown about the functional consequences of this neuronal phenotype and its occurrence across phylogeny (Kim et al, ).…”

Estimating the effect of endogenous dopamine on baseline [11C]‐(+)‐PHNO binding in the human brain

“…Briefly, based on the results of animal studies combining the use of microdialysis and PET, it has been argued that the α‐MPT‐PET paradigm can only quantify DA levels at synaptic D 2/3 R, not extrasynaptic D 2/3 R (Breier et al, ; Kim & Han, ; Laruelle, ). Similarly to the retina (Hirasawa, Contini, & Raviola, ), there is no synaptic DA release into the SN (Bergquist & Nissbrandt, ), nor into the VTA (Adell & Artigas, ; Kalivas & Duffy, ; Omelchenko & Sesack, ). Rather, DA is stored and released extrasynaptically from the dendrites of the SN/VTA (Adell & Artigas, ; Cheramy, Leviel, & Glowinski, ; Geffen, Jessell, Cuello, & Iversen, ; Jaffe, Marty, Schulte, & Chow, ; Korf, Zieleman, M., & Westerink, ; Nieoullon, Cheramy, & Glowinski, ; Wassef, Berod, & Sotelo, ).…”