Cell type- and input-specific differences in the number and subtypes of synaptic GABAA receptors in the hippocampus

Cell type- and input-specific differences in the number and subtypes of synaptic GABAA receptors in the hippocampus
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DOI:
10.1523/jneurosci.22-07-02513.2002
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发表时间:
2002-04-01
影响因子:
5.3
通讯作者:
Somogyi, P
Somogyi, P
中科院分区:
医学1区
文献类型:
--
作者:
Klausberger, T;Roberts, JDB;Somogyi, P

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表达小清蛋白(PV)的篮状细胞网络通过GABA(A)受体介导的突触作用参与不同频率的皮质神经元同步化。这些细胞通过GABA能突触和缝隙连接相互连接,并与不同类型的胆囊收缩素表达的PV阴性篮状细胞会聚到锥体细胞上。为了确定两个篮状细胞群突触的分子特化,我们使用GABA(A)受体的定量电子显微镜免疫金定位。在锥体细胞胞体上由PV阳性篮状细胞形成的突触比PV阴性篮状细胞形成的突触具有高几倍的含α(1)亚基受体的密度,其中大多数是免疫阴性的。在两个突触群体中,β(2/3)亚基的密度相似,表明总体受体密度相似。与锥体细胞上PV阳性篮状细胞形成的突触相比,表达小清蛋白的篮状细胞之间的突触含有高3.6倍的GABA(A)受体(β(2/3)亚基)总密度和高3.2倍的α(1)亚基标记密度。因此,PV阳性篮状细胞主要通过含有α(1)亚基的GABA(A)受体起作用,但受体密度取决于突触后细胞类型。这些观察结果,以及先前报道的PV阴性篮状细胞形成的突触中含有α(2)亚基的受体的富集,表明存在于不同突触群体中的GABA(A)受体的数量和亚型受到突触前和突触后影响的调节。在篮状细胞上的突触中的大量GABA(A)受体可能有助于篮状细胞活动的精确定时定相。
Networks of parvalbumin (PV)-expressing basket cells are implicated in synchronizing cortical neurons at various frequencies, through GABA(A) receptor-mediated synaptic action. These cells are interconnected by GABAergic synapses and gap junctions, and converge with a different class of cholecystokinin-expressing, PV-negative basket cells onto pyramidal cells. To define the molecular specializations in the synapses of the two basket cell populations, we used quantitative electron microscopic immunogold localization of GABA(A) receptors. Synapses formed by PV-positive basket cells on the somata of pyramidal cells had several-fold higher density of alpha(1) subunit-containing receptors than synapses made by PV-negative basket cells, most of which were immunonegative. The density of the beta(2/3) subunits was similar in the two populations of synapse, indicating similar overall receptor density. Synapses interconnecting parvalbumin-expressing basket cells contained a 3.6 times higher overall density of GABA(A) receptor (beta(2/3) subunits) and 3.2 times higher density of alpha(1) subunit labeling compared with synapses formed by boutons of PV-positive basket cells on pyramidal cells. Thus, PV-positive basket cells mainly act through alpha(1) subunit-containing GABA(A) receptors, but the receptor density depends on the postsynaptic cell type. These observations, together with previously reported enrichment of the alpha(2) subunit-containing receptors in synapses made by PV-negative basket cells, indicate that the number and subtypes of GABA(A) receptors present in different synapse populations are regulated by both presynaptic and postsynaptic influences. The high number of GABA(A) receptors in synapses on basket cells might contribute to the precisely timed phasing of basket cell activity.