Altered Localization of the delta Subunit of the GABA(A) Receptor in the Thalamus of alpha 4 Subunit Knockout Mice

作者：Peng Zechun; Zhang Nianhui; Chandra Dave; Homanics Gregg E; Olsen Richard W; Houser Carolyn R^*

来源：Neurochemical Research, 2014, 39(6): 1104-1117.

DOI：10.1007/s11064-013-1202-1

• Immunohistochemistry
• Non-synaptic GABA receptors
• Plasticity
• Receptor trafficking
• Tonic inhibition
• Ventrobasal nucleus

The alpha 4 subunit of the GABA(A) receptor (GABA(A)R) is highly expressed in the thalamus where receptors containing the alpha 4 and delta subunits are major mediators of tonic inhibition. The alpha 4 subunit also exhibits considerable plasticity in a number of physiological and pathological conditions, raising questions about the expression of remaining GABA(A)R subunits when the alpha 4 subunit is absent. Immunohistochemical studies of an alpha 4 subunit knockout (KO) mouse revealed a substantial decrease in delta subunit expression in the ventrobasal nucleus of the thalamus as well as other forebrain regions where the alpha 4 subunit is normally expressed. In contrast, several subunits associated primarily with phasic inhibition, including the alpha 1 and gamma 2 subunits, were moderately increased. Intracellular localization of the delta subunit was also altered. While delta subunit labeling was decreased within the neuropil, some labeling remained in the cell bodies of many neurons in the ventrobasal nucleus. Confocal microscopy demonstrated co-localization of this labeling with an endoplasmic reticulum marker, and electron microscopy demonstrated increased immunogold labeling near the endoplasmic reticulum in the alpha 4 KO mouse. These results emphasize the strong partnership of the delta and alpha 4 subunit in the thalamus and suggest that the alpha 4 subunit of the GABA(A)R plays a critical role in trafficking of the delta subunit to the neuronal surface. The findings also suggest that previously observed reductions in tonic inhibition in the alpha 4 subunit KO mouse are likely to be related to alterations in delta subunit expression, in addition to loss of the alpha 4 subunit.

• 出版日期2014-6