| First Author | Tossell K | Year | 2021 |
| Journal | Eur J Neurosci | Volume | 53 |
| Issue | 6 | Pages | 1722-1737 |
| PubMed ID | 33522050 | Mgi Jnum | J:350381 |
| Mgi Id | MGI:7660872 | Doi | 10.1111/ejn.15133 |
| Citation | Tossell K, et al. (2021) Tonic GABAergic inhibition, via GABA(A) receptors containing alphabetaE subunits, regulates excitability of ventral tegmental area dopamine neurons. Eur J Neurosci 53(6):1722-1737 |
| abstractText | The activity of midbrain dopamine neurons is strongly regulated by fast synaptic inhibitory gamma-Aminobutyric acid (GABA)ergic inputs. There is growing evidence in other brain regions that low concentrations of ambient GABA can persistently activate certain subtypes of GABA(A) receptor to generate a tonic current. However, evidence for a tonic GABAergic current in midbrain dopamine neurons is limited. To address this, we conducted whole-cell recordings from ventral tegmental area (VTA) dopamine neurons in brain slices from mice. We found that application of GABA(A) receptor antagonists decreased the holding current, indicating the presence of a tonic GABAergic input. Global increases in GABA release, induced by either a nitric oxide donor or inhibition of GABA uptake, further increased this tonic current. Importantly, prolonged inhibition of the firing activity of local GABAergic neurons abolished the tonic current. A combination of pharmacology and immunohistochemistry experiments suggested that, unlike common examples of tonic inhibition, this current may be mediated by a relatively unusual combination of alpha4betaE subunits. Lastly, we found that the tonic current reduced excitability in dopamine neurons suggesting a subtractive effect on firing activity. |
