Activity-Dependent Transmission and Integration Control the Timescales of Auditory Processing at an Inhibitory Synapse
Activity-Dependent Transmission and Integration Control the Timescales of Auditory Processing at an Inhibitory Synapse
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DOI：
10.1016/j.cub.2015.04.026
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发表时间：
2015-06-15
期刊：
影响因子：
9.2
通讯作者：
Felmy, Felix
中科院分区：
文献类型：
--
作者：
Ammer, Julian. J.;Siveke, Ida;Felmy, Felix
为了捕捉感官信息的上下文，神经网络必须在多个时间尺度上处理输入信号。在听觉系统中，外侧丘系背核（DNLL）中的抑制性GABA能突触发生了时间处理的显著变化。在这个突触上，抑制比刺激持续数十毫秒，因此它抑制了对滞后声音的反应，因此与回声抑制有关。在这里，我们解开这种抑制的细胞基础。我们证明了在体内全细胞膜片钳记录在蒙古沙鼠的抑制持续时间增加与声音强度。在急性切片记录中，活动依赖性溢出和异步释放将体内发现的高突触前放电率转化为延长的突触输出。控制抑制时程的一个关键机制是超极化抑制电导的被动整合。这种延长依赖于突触传导幅度。计算模型表明，这种延长是一种普遍的机制，并依赖于一个非线性效应所造成的突触电导饱和时，接近GABA逆转电位。由此产生的超极化产生有效的活动依赖性抑制动作电位，而不影响输入-输出功能的阈值或增益。总之，DNLL中的GABA能抑制通过抑制与活性依赖性突触动力学的被动整合而调节至生理学相关的持续时间。处理时间尺度的这种变化与DNLL之间的相互连接性相结合，实现了抑制回声的分散注意力的定位线索的机制，并有助于可靠地定位初始声源。
To capture the context of sensory information, neural networks must process input signals across multiple timescales. In the auditory system, a prominent change in temporal processing takes place at an inhibitory GABAergic synapse in the dorsal nucleus of the lateral lemniscus (DNLL). At this synapse, inhibition outlasts the stimulus by tens of milliseconds, such that it suppresses responses to lagging sounds, and is therefore implicated in echo suppression. Here, we untangle the cellular basis of this inhibition. We demonstrate with in vivo whole-cell patch-clamp recordings in Mongolian gerbils that the duration of inhibition increases with sound intensity. Activity-dependent spillover and asynchronous release translate the high presynaptic firing rates found in vivo into a prolonged synaptic output in acute slice recordings. A key mechanism controlling the inhibitory time course is the passive integration of the hyperpolarizing inhibitory conductance. This prolongation depends on the synaptic conductance amplitude. Computational modeling shows that this prolongation is a general mechanism and relies on a non-linear effect caused by synaptic conductance saturation when approaching the GABA reversal potential. The resulting hyperpolarization generates an efficient activity-dependent suppression of action potentials without affecting the threshold or gain of the input-output function. Taken together, the GABAergic inhibition in the DNLL is adjusted to the physiologically relevant duration by passive integration of inhibition with activity-dependent synaptic kinetics. This change in processing timescale combined with the reciprocal connectivity between the DNLLs implements a mechanism to suppress the distracting localization cues of echoes and helps to localize the initial sound source reliably.