| First Author | Rosas-Arellano A | Year | 2018 |
| Journal | Neurobiol Dis | Volume | 110 |
| Pages | 142-153 | PubMed ID | 29196217 |
| Mgi Jnum | J:259753 | Mgi Id | MGI:6142061 |
| Doi | 10.1016/j.nbd.2017.11.010 | Citation | Rosas-Arellano A, et al. (2018) Huntington's disease leads to decrease of GABA-A tonic subunits in the D2 neostriatal pathway and their relocalization into the synaptic cleft. Neurobiol Dis 110:142-153 |
| abstractText | GABA is a widely distributed inhibitory neurotransmitter. GABA-A receptors are hetero-pentameric channels assembled in multiple combinations from 19 available subunits; this diversity mediates phasic and tonic inhibitory synaptic potentials. Whereas GABA-A phasic receptors are located within the synaptic cleft, GABA-A tonic receptors are found peri- or extra-synaptically, where they are activated by diffusion of synaptic GABA release. In the neostriatum, GABA-A tonic subunits are present in the D2 medium-size spiny neurons. Since early impairment of these neurons is observed in Huntington''s disease, we determined the ultrastructural localization of GABA-A-alpha5, -beta3, -delta, -rho2 and, for the first time, of GABA-A-rho3 subunits, in the D2 pathway of the YAC128 murine model of Huntington''s disease at various stages of disease progression. We report mislocalization of all five subunits from peri- and extra-synaptic spaces into the synaptic clefts of YAC128 mice, present in diseased mice as early as 6 months-old. The synaptic localization of GABA-A tonic receptors correlated with increased sensitivity to pharmacologic antagonists during extracellular electrophysiological recordings in neostriatal slices. Finally, the association of GABA-A tonic receptors with the D2 pathway in 6-month-old mice was largely lost at 12 months of age. |
