Quinn Dylan P, Kolar Annette, Harris Sydney A, Wigerius Michael, Fawcett James P, Krueger Stefan R
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Front Cell Neurosci. 2019 Jun 27;13:291. doi: 10.3389/fncel.2019.00291. eCollection 2019.
Neuronal activity is thought to drive the remodeling of circuits in the mammalian cerebral cortex. However, its precise function in the underlying formation and elimination of glutamatergic synapses has remained controversial. To clarify the role of activity in synapse turnover, we have assessed the effects of inhibition of glutamate release from a sparse subset of cultured hippocampal neurons on synapse turnover. Sustained chemogenetic attenuation of release through presynaptic expression of a designer receptor exclusively activated by designer drugs (DREADD) had no effect on the formation or elimination of glutamatergic synapses. Sparse expression of tetanus neurotoxin light chain (TeNT-LC), a synaptobrevin-cleaving protease that completely abolishes neurotransmitter release, likewise did not lead to changes in the rate of synapse elimination, although it reduced the rate of synapse formation. The stability of active and silenced synapses correlated with measures of synapse size. While not excluding a modulatory role in synapse elimination, our findings show that synaptic activity is neither required for the removal nor the maintenance of glutamatergic synapses between hippocampal neurons. Our results also demonstrate that the stability of glutamatergic synapses scales with their size irrespective of their activity.
神经元活动被认为驱动哺乳动物大脑皮质中神经回路的重塑。然而，其在谷氨酸能突触形成与消除这一基础过程中的精确功能仍存在争议。为阐明活动在突触更新中的作用，我们评估了抑制培养的海马神经元稀疏亚群中谷氨酸释放对突触更新的影响。通过仅由设计药物激活的设计受体（DREADD）在突触前表达来持续化学遗传减弱释放，对谷氨酸能突触的形成或消除没有影响。破伤风神经毒素轻链（TeNT-LC）是一种切割突触小泡蛋白的蛋白酶，可完全消除神经递质释放，其稀疏表达同样未导致突触消除速率的变化，尽管它降低了突触形成速率。活跃和沉默突触的稳定性与突触大小的测量值相关。虽然不排除在突触消除中起调节作用，但我们的研究结果表明，突触活动对于海马神经元之间谷氨酸能突触的消除和维持既不是必需的。我们的结果还表明，谷氨酸能突触的稳定性与其大小成比例，而与它们的活动无关。
