Short-term depression of external globus pallidus-subthalamic nucleus synaptic transmission and implications for patterning subthalamic activity.
Short-term depression of external globus pallidus-subthalamic nucleus synaptic transmission and implications for patterning subthalamic activity.
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DOI：
10.1523/jneurosci.3576-12.2013
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发表时间：
2013-04-24
期刊：
影响因子：
--
通讯作者：
Bevan MD
中科院分区：
文献类型：
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作者：
Atherton JF;Menard A;Urbain N;Bevan MD
GABA能苍白球外侧核（GPe）和丘脑底核（BNZ）的活动频率和方式与运动功能密切相关。虽然阶段性的，单一的GPe-ESTA输入强大的模式ESTA活动离体，相关的GPe-ESTA活动通常不会在体内观察到。为了检验GPe的影响受到短期突触抑制的约束这一假设，在大鼠和小鼠脑切片中以模仿GPe体内活性的速率和模式刺激单一GPe-TdR输入。这些数据与连通性估计一起用于模拟GPe-GPRS传输。单一的GPe-突触连接最初产生大的电导和可靠的传输。然而，当以体内GPe活动的平均速率（33 Hz）刺激连接时，传输的幅度和可靠性迅速下降（τ = 0.6 ± 0.5 s）至其初始值的<10%。从抑郁状态恢复（τ = 17.3 ± 18.9 s）的时间也长于体内紧张性GPe活性的暂停时间。抑郁症是由于供应有限的释放准备囊泡，并在鲜明的对比，举行的传递，表现出100%的可靠性。注射模拟GPe-β传导显示，突触抑制引起紧张，非同步GPe-β活动破坏，而不是取消自主的β活动。此外，同步抑制紧张性活动的GPe-ESTA神经元或GPe-ESTA神经元的阶段性活动可靠模式ESTA活动，通过解除抑制和抑制，分别。总之，这些数据表明，GPe活动的频率和模式深刻地影响了它向大脑的传输。
The frequency and pattern of activity in the reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN) are closely related to motor function. Although phasic, unitary GPe-STN inputs powerfully pattern STN activity ex vivo, correlated GPe-STN activity is not normally observed in vivo. To test the hypothesis that the GPe’s influence is constrained by short-term synaptic depression, unitary GPe-STN inputs were stimulated in rat and mouse brain slices at rates and in patterns that mimicked GPe activity in vivo. Together with connectivity estimates these data were then used to simulate GPe-STN transmission. Unitary GPe-STN synaptic connections initially generated large conductances and transmitted reliably. However, the amplitude and reliability of transmission declined rapidly (τ = 0.6 ± 0.5 s) to <10% of their initial values when connections were stimulated at the mean rate of GPe activity in vivo (33 Hz). Recovery from depression (τ = 17.3 ± 18.9 s) was also longer than pauses in tonic GPe activity in vivo. Depression was due to limited supply of release-ready vesicles and was in sharp contrast to Calyx of Held transmission, which exhibited 100% reliability. Injection of simulated GPe-STN conductances revealed that synaptic depression caused tonic, non-synchronized GPe-STN activity to disrupt rather than abolish autonomous STN activity. Furthermore, synchronous inhibition of tonically active GPe-STN neurons or phasic activity of GPe-STN neurons reliably patterned STN activity through disinhibition and inhibition, respectively. Together these data argue that the frequency and pattern of GPe activity profoundly influences its transmission to the STN.