Divergent Properties and Independent Regulation of Striatal Dopamine and GABA Co-transmission

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 May 18

PMID 35584679

Authors

Sarah M Zych

Christopher P Ford

Affiliations

Soon will be listed here.

Abstract

Substantia nigra pars compacta (SNc) dopamine neurons play a key role in regulating the activity of striatal circuits within the basal ganglia. In addition to dopamine, these neurons release several other transmitters, including the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Both dopamine and GABA are loaded into SNc synaptic vesicles by the vesicular monoamine transporter 2 (VMAT2), and co-release of GABA provides strong inhibition to the striatum by directly inhibiting striatal medium spiny projection neurons (MSNs) through activation of GABA receptors. Here, we found that despite both dopamine and GABA being co-packaged by VMAT2, the properties of transmission, including Ca sensitivity, release probability, and requirement of active zone scaffolding proteins, differ between the two transmitters. Moreover, the extent by which presynaptic neuromodulators inhibit co-transmission also varied. Differences in modulation and the mechanisms controlling release allow for independent regulation of dopamine and GABA signals despite both being loaded via similar mechanisms.

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References

Egana L, Cuevas R, Baust T, Parra L, Leak R, Hochendoner S . Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3. J Neurosci. 2009; 29(14):4592-604. PMC: 2846176. DOI: 10.1523/JNEUROSCI.4559-08.2009. View

Melani R, Tritsch N . Inhibitory co-transmission from midbrain dopamine neurons relies on presynaptic GABA uptake. Cell Rep. 2022; 39(3):110716. PMC: 9097974. DOI: 10.1016/j.celrep.2022.110716. View

Descarries L, WATKINS K, Garcia S, Bosler O, DOUCET G . Dual character, asynaptic and synaptic, of the dopamine innervation in adult rat neostriatum: a quantitative autoradiographic and immunocytochemical analysis. J Comp Neurol. 1996; 375(2):167-86. DOI: 10.1002/(SICI)1096-9861(19961111)375:2<167::AID-CNE1>3.0.CO;2-0. View

Tsudzuki T, Tsujita M . Isoosmotic isolation of rat brain synaptic vesicles, some of which contain tyrosine hydroxylase. J Biochem. 2004; 136(2):239-43. DOI: 10.1093/jb/mvh113. View

Eggermann E, Bucurenciu I, Goswami S, Jonas P . Nanodomain coupling between Ca²⁺ channels and sensors of exocytosis at fast mammalian synapses. Nat Rev Neurosci. 2011; 13(1):7-21. PMC: 3617475. DOI: 10.1038/nrn3125. View

Jaffe E, Marty A, Schulte A, Chow R . Extrasynaptic vesicular transmitter release from the somata of substantia nigra neurons in rat midbrain slices. J Neurosci. 1998; 18(10):3548-53. PMC: 6793140. View

Betz A, Thakur P, Junge H, Ashery U, Rhee J, Scheuss V . Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 2001; 30(1):183-96. DOI: 10.1016/s0896-6273(01)00272-0. View

Sungkaworn T, Jobin M, Burnecki K, Weron A, Lohse M, Calebiro D . Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots. Nature. 2017; 550(7677):543-547. DOI: 10.1038/nature24264. View

Chen B, Rice M . Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum. J Neurosci. 2001; 21(19):7841-7. PMC: 6762877. View

10.

Joyce M, Rayport S . Mesoaccumbens dopamine neuron synapses reconstructed in vitro are glutamatergic. Neuroscience. 2000; 99(3):445-56. DOI: 10.1016/s0306-4522(00)00219-0. View

11.

Markwardt S, Wadiche J, Overstreet-Wadiche L . Input-specific GABAergic signaling to newborn neurons in adult dentate gyrus. J Neurosci. 2009; 29(48):15063-72. PMC: 2846629. DOI: 10.1523/JNEUROSCI.2727-09.2009. View

12.

Marcott P, Mamaligas A, Ford C . Phasic dopamine release drives rapid activation of striatal D2-receptors. Neuron. 2014; 84(1):164-176. PMC: 4325987. DOI: 10.1016/j.neuron.2014.08.058. View

13.

Touhara K, MacKinnon R . Molecular basis of signaling specificity between GIRK channels and GPCRs. Elife. 2018; 7. PMC: 6335053. DOI: 10.7554/eLife.42908. View

14.

Imig C, Min S, Krinner S, Arancillo M, Rosenmund C, Sudhof T . The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones. Neuron. 2014; 84(2):416-31. DOI: 10.1016/j.neuron.2014.10.009. View

15.

Fortin G, Ducrot C, Giguere N, Kouwenhoven W, Bourque M, Pacelli C . Segregation of dopamine and glutamate release sites in dopamine neuron axons: regulation by striatal target cells. FASEB J. 2018; 33(1):400-417. DOI: 10.1096/fj.201800713RR. View

16.

Camacho M, Basu J, Trimbuch T, Chang S, Pulido-Lozano C, Chang S . Heterodimerization of Munc13 CA domain with RIM regulates synaptic vesicle docking and priming. Nat Commun. 2017; 8:15293. PMC: 5436228. DOI: 10.1038/ncomms15293. View

17.

Silm K, Yang J, Marcott P, Asensio C, Eriksen J, Guthrie D . Synaptic Vesicle Recycling Pathway Determines Neurotransmitter Content and Release Properties. Neuron. 2019; 102(4):786-800.e5. PMC: 6541489. DOI: 10.1016/j.neuron.2019.03.031. View

18.

Peter D, Jimenez J, Liu Y, Kim J, EDWARDS R . The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. J Biol Chem. 1994; 269(10):7231-7. View

19.

Li M, Bermak J, Wang Z, Zhou Q . Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280). Mol Pharmacol. 2000; 57(3):446-52. DOI: 10.1124/mol.57.3.446. View

20.

Ford C, Gantz S, Phillips P, Williams J . Control of extracellular dopamine at dendrite and axon terminals. J Neurosci. 2010; 30(20):6975-83. PMC: 2883253. DOI: 10.1523/JNEUROSCI.1020-10.2010. View