Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8.
J Neurosci. 2011 Sep 21;31(38):13386-99. doi: 10.1523/JNEUROSCI.0400-11.2011.
Reliable neuronal spiking is critical for a myriad of computations performed by neural circuits. This is particularly evident for sound localization cues in the auditory brainstem circuits that detect timing and intensity differences of sounds arriving at two ears. The calyx of Held-principal neuron synapse in the medial nucleus of the trapezoid body (MNTB) in this circuit is traditionally viewed as a reliable relay, which converts contralateral excitatory inputs to inhibitory outputs to ipsilateral superior olive neurons that code interaural timing and intensity differences. However, recent studies demonstrated large variability in the incidence of postsynaptic spike failures at this synapse, challenging the view that this synapse is a fail-safe relay. Using combined imaging and paired recordings in mature (P16-P19) mouse brainstem slices, we show that spike failure rates of MNTB neurons are strongly correlated with differences in gross morphology of the calyx terminal and quantal properties under standard in vitro- and in vivo-like conditions. MNTB neurons innervated by calyces with simple morphologies (mainly digits) express strong short-term synaptic depression and a high incidence of spike failures after high-frequency stimulation. Conversely, MNTB neurons innervated by structurally complex calyces (digits and numerous bouton-like swellings) exhibit initial facilitation followed by slow depression and very few spike failures. Our results indicate that the calyx of Held-MNTB synapse is likely organized as a structural and functional continuum, in that correlated heterogeneities in calyx morphology and short-term plasticity serve as a filter for regulating the inhibition delivered to superior olive neurons during sound localization.
可靠的神经元发放对于神经回路执行的众多计算至关重要。这在听觉脑干回路中检测到达两只耳朵的声音的时间和强度差异的声音定位线索中尤为明显。该回路中的斜方体核内终球-主神经元突触的 Held 终球-主神经元突触传统上被视为可靠的中继，它将对侧兴奋性输入转换为抑制性输出，传递到同侧上橄榄神经元，以编码两耳时间和强度差异。然而，最近的研究表明，在这个突触后神经元发放失败的发生率存在很大的可变性，这对这个突触是一个安全的中继的观点提出了挑战。使用成熟（P16-P19）小鼠脑干切片中的联合成像和配对记录，我们表明 MNTB 神经元的发放失败率与终球末端的总形态和标准体外和体内样条件下的量子特性差异密切相关。由形态简单（主要是指状结构）的终球支配的 MNTB 神经元表达强烈的短期突触抑制和在高频刺激后发放失败的高发生率。相反，由结构复杂的终球（指状结构和众多小球状肿胀）支配的 MNTB 神经元表现出初始易化，随后是缓慢的抑制和很少的发放失败。我们的结果表明，Held 终球-MNTB 突触可能作为一个结构和功能的连续体组织，因为终球形态和短期可塑性的相关异质性作为调节声音定位时传递到上橄榄神经元的抑制的过滤器。
