The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
J Physiol. 2011 Dec 1;589(Pt 23):5649-62. doi: 10.1113/jphysiol.2011.213702. Epub 2011 Sep 19.
Synaptic refinement, a process that involves elimination and strengthening of immature synapses, is critical for the development of neural circuits and behaviour. The present study investigates the role of adenylate cyclase 1 (AC1) in developmental refinement of excitatory synapses in the thalamus at the single-cell level. In the mouse, thalamic relay synapses of the lemniscal pathway undergo extensive remodelling during the second week after birth, and AC1 is highly expressed in both pre- and postsynaptic neurons during this period. Synaptic connectivity was analysed by patch-clamp recording in acute slices obtained from mice carrying a targeted null mutation of the adenylate cyclase 1 gene (AC1-KO) and wild-type littermates. We found that deletion of AC1 had no effect on the number of relay inputs received by thalamic neurons during development. In contrast, there was a selective reduction of AMPA-receptor-mediated synaptic responses in mutant thalamic neurons, and the effect increased with age. Furthermore, experience-dependent plasticity was impaired in thalamic neurons of AC1-KO mice. Whisker deprivation during early life altered the number and properties of relay inputs received by thalamic neurons in wild-type mice, but had no effects in AC1-KO mice. Our findings underline a role for AC1 in experience-dependent plasticity of excitatory synapses.
突触修正，这一涉及不成熟突触消除和强化的过程，对神经回路和行为的发育至关重要。本研究在单细胞水平上研究了腺苷酸环化酶 1 (AC1) 在丘脑兴奋性突触发育修正中的作用。在小鼠中，丘觉的投射通路的中继突触在出生后第二周经历了广泛的重塑，在此期间，AC1 在突触前和突触后神经元中均高度表达。通过对携带腺苷酸环化酶 1 基因（AC1-KO）靶向缺失突变的小鼠和野生型同窝仔鼠的急性切片进行膜片钳记录，分析了突触连接。我们发现，AC1 的缺失对丘脑神经元在发育过程中接收的中继输入数量没有影响。相比之下，在突变体丘脑神经元中，AMPA 受体介导的突触反应选择性减少，并且这种影响随着年龄的增长而增加。此外，AC1-KO 小鼠的丘脑神经元的经验依赖性可塑性受损。在生命早期剥夺胡须会改变野生型小鼠中丘脑神经元接收的中继输入的数量和特性，但在 AC1-KO 小鼠中没有影响。我们的研究结果强调了 AC1 在兴奋性突触的经验依赖性可塑性中的作用。
