State University of New York at Stony Brook, 11794-5230, USA.
J Comp Neurol. 2010 Dec 15;518(24):4842-54. doi: 10.1002/cne.22491.
GABAergic interneurons are key elements regulating the activity of local circuits, and abnormal inhibitory circuits are implicated in certain psychiatric and neurodevelopmental diseases. The glutamatergic input that interneurons receive is a key determinant of their activity, yet its molecular structure and development, which are often distinct from those of glutamatergic input to pyramidal cells, are poorly defined. The membrane-associated guanylate kinase (MAGUK) homologs PSD-95/SAP90, PSD-93/chapsyn110, SAP97, and SAP102 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons. We therefore studied the cell-type-specific and developmental expression of MAGUKs in the nonoverlapping parvalbumin (PV)- and somatostatin (SOM)-positive interneurons in the visual cortex. These interneuron subtypes account for the vast majority of interneurons in the cortex and have different functional properties and postsynaptic structures, being either axodendritic (PV(+)) or axospinous (SOM(+)). To study cell-type-specific MAGUK expression, we used DIG-labeled riboprobes against each MAGUK along with antibodies against either PV or SOM and examined tissue from juvenile (P15) and adult mice. Both PV(+) and SOM(+) interneurons express mRNA for PSD-95, PSD-93, and SAP102 in P15 and adult tissue. In contrast, these interneuron subtypes express SAP97 at P15, but for adult visual cortex we found that most PV(+) and SOM(+) interneurons show low or no expression of SAP97. Given the importance of SAP97 in regulating AMPA receptor GluA1 subunit and NMDA receptor subunits at glutamatergic synapses, these results suggest a developmental shift in glutamate receptor subunit composition and regulation of glutamatergic synapses on PV(+) and SOM(+) interneurons.
GABA 能中间神经元是调节局部回路活动的关键因素，异常抑制回路与某些精神和神经发育疾病有关。中间神经元接受的谷氨酸能输入是其活动的关键决定因素，但其分子结构和发育通常与锥体神经元的谷氨酸能输入不同，因此定义不明确。膜相关鸟苷酸激酶 (MAGUK) 同源物 PSD-95/SAP90、PSD-93/chapsyn110、SAP97 和 SAP102 是锥体神经元兴奋性突触后密度的核心组织者。因此，我们研究了 MAGUK 在视觉皮层中不重叠的 Parvalbumin (PV)-和 Somatostatin (SOM)-阳性中间神经元中的细胞类型特异性和发育表达。这些中间神经元亚型占皮层中间神经元的绝大多数，具有不同的功能特性和突触后结构，要么是轴突树突 (PV(+)) 要么是轴突棘 (SOM(+))。为了研究细胞类型特异性 MAGUK 表达，我们使用针对每个 MAGUK 的 DIG 标记的 RNA 探针，以及针对 PV 或 SOM 的抗体，检查了幼年 (P15) 和成年小鼠的组织。在 P15 和成年组织中，PV(+)和 SOM(+)中间神经元均表达 PSD-95、PSD-93 和 SAP102 的 mRNA。相比之下，这些中间神经元亚型在 P15 时表达 SAP97，但对于成年视觉皮层，我们发现大多数 PV(+)和 SOM(+)中间神经元的 SAP97 表达水平较低或没有。鉴于 SAP97 在调节谷氨酸能突触处的 AMPA 受体 GluA1 亚基和 NMDA 受体亚基中的重要性，这些结果表明 PV(+)和 SOM(+)中间神经元上的谷氨酸能突触的谷氨酸受体亚基组成和调节存在发育性转变。
