Synaptotagmin 7 confers frequency invariance onto specialized depressing synapses.
Synaptotagmin 7 confers frequency invariance onto specialized depressing synapses.
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DOI：
10.1038/nature24474
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发表时间：
2017-11-23
期刊：
影响因子：
64.8
通讯作者：
Regehr WG
中科院分区：
文献类型：
--
作者：
Turecek J;Jackman SL;Regehr WG
在大脑中的大多数突触，短期可塑性动态地调节突触强度。突触强度的快速频率依赖性变化在感觉适应、增益控制和许多其他神经计算中起着关键作用。然而，一些听觉、前庭和小脑突触在广泛的放电频率范围内保持恒定的强度，因此有效地编码了放电频率。尽管表面上看起来很简单，但由于固有的突触非线性，频率不变的传输很难实现。在这里，我们研究了浦肯野细胞到小脑深核(PC到DCN)突触和前庭突触的频率不变传递。这些突触的长时间激活导致最初的抑郁，紧随其后的是稳态反应，这些反应在其生理活动范围内是频率不变的。我们发现，突触素7(Syt7)，一种最近发现的短期易化钙传感器，存在于这两个突触中。目前尚不清楚为什么在这些和其他令人沮丧的突触上会出现促进作用的传感器。我们发现，在PC和前庭突触，Syt7支持一个隐藏的促进成分，这种成分在野生型动物中可以被揭开，但在Syt7基因敲除动物中不存在。在野生型小鼠中，易化性随着发射频率的增加而增加，并抵消抑制以产生频率不变的传递。在Syt7基因敲除小鼠中，PC和前庭突触表现出传统的使用依赖性抑制，随着放电频率的增加，抑制程度更大。突触前挽救Syt7的表达可以恢复易化和频率不变的传递。我们的结果确定了Syt7在突触上表现出全面抑制的功能，并证明了易化在产生频率不变的传递中发挥着意想不到的重要作用。
At most synapses in the brain, short-term plasticity dynamically modulates synaptic strength. Rapid frequency-dependent changes in synaptic strength play critical roles in sensory adaptation, gain control and many other neural computations. However, some auditory, vestibular and cerebellar synapses maintain constant strength over a wide range of firing frequencies, and as a result efficiently encode firing rates. Despite its apparent simplicity, frequency-invariant transmission is difficult to achieve because of inherent synaptic nonlinearities. Here we study frequency-invariant transmission at Purkinje cell to deep cerebellar nuclear (PC to DCN) synapses and vestibular synapses. Prolonged activation of these synapses leads to initial depression, which is followed by steady-state responses that are frequency invariant for their physiological activity range. We find that Synaptotagmin 7 (Syt7), a recently identified calcium sensor for short-term facilitation, is present at both synapses. It was unclear why a sensor for facilitation would be present at these and other depressing synapses. We find that at PC and vestibular synapses, Syt7 supports a hidden component of facilitation that can be unmasked in wildtype animals but is absent in Syt7 knockout animals. In wildtype mice, facilitation increases with firing frequency and counteracts depression to produce frequency-invariant transmission. In Syt7 knockout mice, PC and vestibular synapses exhibit conventional use-dependent depression, weakening to a greater extent as the firing frequency is increased. Presynaptic rescue of Syt7 expression restores both facilitation and frequency-invariant transmission. Our results identify a function for Syt7 at synapses that exhibit overall depression, and demonstrate that facilitation plays an unexpected and important role in producing frequency-invariant transmission.
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64.8
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Bakken TE;Miller JA;Ding SL;Sunkin SM;Smith KA;Ng L;Szafer A;Dalley RA;Royall JJ;Lemon T;Shapouri S;Aiona K;Arnold J;Bennett JL;Bertagnolli D;Bickley K;Boe A;Brouner K;Butler S;Byrnes E;Caldejon S;Carey A;Cate S;Chapin M;Chen J;Dee N;Desta T;Dolbeare TA;Dotson N;Ebbert A;Fulfs E;Gee G;Gilbert TL;Goldy J;Gourley L;Gregor B;Gu G;Hall J;Haradon Z;Haynor DR;Hejazinia N;Hoerder-Suabedissen A;Howard R;Jochim J;Kinnunen M;Kriedberg A;Kuan CL;Lau C;Lee CK;Lee F;Luong L;Mastan N;May R;Melchor J;Mosqueda N;Mott E;Ngo K;Nyhus J;Oldre A;Olson E;Parente J;Parker PD;Parry S;Pendergraft J;Potekhina L;Reding M;Riley ZL;Roberts T;Rogers B;Roll K;Rosen D;Sandman D;Sarreal M;Shapovalova N;Shi S;Sjoquist N;Sodt AJ;Townsend R;Velasquez L;Wagley U;Wakeman WB;White C;Bennett C;Wu J;Young R;Youngstrom BL;Wohnoutka P;Gibbs RA;Rogers J;Hohmann JG;Hawrylycz MJ;Hevner RF;Molnár Z;Phillips JW;Dang C;Jones AR;Amaral DG;Bernard A;Lein ES
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