Balland Bénédicte, Lachamp Philippe, Strube Caroline, Kessler Jean-Pierre, Tell Fabien
Laboratoire de Neurophysiologie Cellulaire, CNRS UMR 6150, IFR Jean-Roche, Faculté de Médecine, Bd Pierre Dramard, 13916 Marseille cedex 20, France.
J Physiol. 2006 Jul 1;574(Pt 1):245-61. doi: 10.1113/jphysiol.2006.108738. Epub 2006 May 11.
Calcium influxes through ionotropic glutamate receptors (AMPA and NMDA receptors, AMPARs and NMDARs) are considered to be critical for the shaping and refinement of neural circuits during synaptogenesis. Using a combined morphological and electrophysiological approach, we evaluated this hypothesis at the level of the nucleus tractus solitarii (NTS), a brainstem structure that is a gateway for many visceral sensory afferent fibres. We confirmed that in the NTS, the first excitatory synapses appeared at embryonic day 18. We next characterized the biophysical properties of NTS AMPARs. Throughout perinatal development, both evoked and miniature EPSCs recorded in the presence of an NMDAR blocker were insensitive to polyamines and had linear current-voltage relationships. This demonstrated that AMPARs at NTS excitatory synapses were calcium-impermeable receptors composed of a majority of GluR2 subunits. We then investigated the influence of calcium influxes through NMDARs on the development of NTS synaptic transmission. We found that NMDAR expression at synaptic sites did not precede AMPAR expression. Moreover, NMDAR blockade in utero did not prevent the development of AMPAR synaptic currents and the synaptic clustering of GluR2 subunits. Thus, our data support an alternative model of synaptogenesis that does not depend on calcium influxes through either AMPARs or NMDARs. This model may be particularly relevant to the formation of neural networks devoted to basic behaviours required at birth for survival.
通过离子型谷氨酸受体(AMPA和NMDA受体,即AMPARs和NMDARs)的钙内流被认为在突触发生过程中对神经回路的形成和精细化至关重要。我们采用形态学和电生理学相结合的方法,在孤束核(NTS)水平评估了这一假说,孤束核是脑干结构,是许多内脏感觉传入纤维的通道。我们证实,在NTS中,第一批兴奋性突触出现在胚胎第18天。接下来,我们对NTS的AMPARs的生物物理特性进行了表征。在围产期发育过程中,在存在NMDAR阻滞剂的情况下记录的诱发型和微小兴奋性突触后电流(EPSCs)对多胺不敏感,并且具有线性电流-电压关系。这表明NTS兴奋性突触处的AMPARs是由大多数GluR2亚基组成的钙不渗透受体。然后,我们研究了通过NMDARs的钙内流对NTS突触传递发育的影响。我们发现突触部位的NMDAR表达并不先于AMPAR表达。此外,子宫内NMDAR阻断并不妨碍AMPAR突触电流的发育以及GluR2亚基的突触聚集。因此,我们的数据支持一种不依赖于通过AMPARs或NMDARs的钙内流的突触发生替代模型。该模型可能与致力于出生时生存所需基本行为的神经网络的形成特别相关。