Distinct roles of synaptic and extrasynaptic GABA(A) receptors in striatal inhibition dynamics

作者：Luo Ruixi; Partridge John G; Vicini Stefano^*

来源：Frontiers in Neural Circuits, 2013, 7: 186.

DOI：10.3389/fncir.2013.00186

• GABA
• tonic inhibition
• striatum
• patch-clamp
• Cre-lox genetics

Striatonigral and striatopallidal projecting medium spiny neurons (MSNs) express dopamine D1 (D1+) and D2 receptors (D2+), respectively. Both classes receive extensive GABAergic input via expression of synaptic, perisynaptic, and extrasynaptic GABA(A) receptors. The activation patterns of different presynaptic GABAergic neurons produce transient and sustained GABA(A) receptor-mediated conductance that fulfill distinct physiological roles. We performed single and dual whole cell recordings from striatal neurons in mice expressing fluorescent proteins in interneurons and MSNs. We report specific inhibitory dynamics produced by distinct activation patterns of presynaptic GABAergic neurons as source of synaptic, perisynaptic, and extrasynaptic inhibition. Synaptic GABA(A) receptors in MSNs contain the alpha 2, gamma 2, and a beta subunit. In addition, there is evidence for the developmental increase of the alpha 1 subunit that contributes to faster inhibitory post-synaptic current (IPSC). Tonic GABAergic currents in MSNs from adult mice are carried by extrasynaptic receptors containing the alpha 4 and delta subunit, while in younger mice this current is mediated by receptors that contain the alpha 5 subunit. Both forms of tonic currents are differentially expressed in D1+ and D2+ MSNs. This study extends these findings by relating presynaptic activation with pharmacological analysis of inhibitory conductance in mice where the beta 3 subunit is conditionally removed in fluorescently labeled D2+ MSNs and in mice with global deletion of the delta subunit. Our results show that responses to low doses of gaboxadol (2 mu M), a GABA(A) receptor agonist with preference to delta subunit, are abolished in the delta but not the beta 3 subunit knock out mice. This suggests that the beta 3 subunit is not a component of the adult extrasynaptic receptor pool, in contrast to what has been shown for tonic current in young mice. Deletion of the beta 3 subunit from D2+ MSNs however, removed slow spontaneous IPSCs, implicating its role in mediating synaptic input from striatal neurogliaform interneurons.

• 出版日期2013-11-26