Zhao H M, Wenthold R J, Petralia R S
National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 1998 Jul 15;18(14):5517-28. doi: 10.1523/JNEUROSCI.18-14-05517.1998.
Selective targeting of neurotransmitter receptors to specific synapse populations occurs in adult neurons, but little is known about the development of these receptor distribution patterns. In this study, we demonstrate that a specific developmental switch occurs in the targeting of a receptor to an identified synapse population. Localization of delta and AMPA glutamate receptors at parallel and climbing fiber synapses on the developing Purkinje cells was studied using postembedding immunogold. Delta receptors were found to be abundant on postsynaptic membranes at parallel fiber synapses from postnatal day 10 (P10) to adult. In contrast, delta receptors were found to be high at climbing fiber synapses only at P10 and P14. Thus, a major finding of this paper is that high levels of delta receptors are transiently expressed in climbing fiber synapses in the second postnatal week. Labeling of synapses with anti-delta receptor antibody at P10 was limited to the postsynaptic membrane of excitatory synapses and was absent from GABAergic synapses. Unlike delta receptor immunolabeling, AMPA receptor immunolabeling (GluR2/3 and GluR2 antibodies) was high in the postsynaptic membranes of synapses at early postnatal ages (P2 and P5) and was higher in climbing fiber synapses than in parallel fiber synapses from P10 to adult. The present study shows that synapse-specific targeting of glutamate receptors in Purkinje cells is developmentally regulated, with the postsynaptic receptor composition established during synapse maturation. This composition is not dependent on the nature of the initial establishment of synaptic connections.
在成年神经元中,神经递质受体可选择性地靶向特定的突触群,但对于这些受体分布模式的发育过程却知之甚少。在本研究中,我们证明了在将一种受体靶向特定突触群的过程中会发生特定的发育转变。利用包埋后免疫金法研究了发育中的浦肯野细胞上平行纤维和攀缘纤维突触处δ和AMPA谷氨酸受体的定位。发现从出生后第10天(P10)到成年,δ受体在平行纤维突触的突触后膜上大量存在。相比之下,仅在P10和P14时,δ受体在攀缘纤维突触处含量较高。因此,本文的一个主要发现是,在出生后第二周,高水平的δ受体在攀缘纤维突触中短暂表达。在P10时,用抗δ受体抗体标记突触仅限于兴奋性突触的突触后膜,而GABA能突触中则没有。与δ受体免疫标记不同,AMPA受体免疫标记(GluR2/3和GluR2抗体)在出生后早期(P2和P5)突触的突触后膜中含量较高,并且从P10到成年,在攀缘纤维突触中的含量高于平行纤维突触。本研究表明,浦肯野细胞中谷氨酸受体的突触特异性靶向是受发育调控的,突触后受体组成在突触成熟过程中确立。这种组成不依赖于突触连接初始建立的性质。