Wu Shuting, Wardak Asem, Khan Mehak M, Chen Christopher H, Regehr Wade G
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv. 2023 May 25:2023.05.25.542308. doi: 10.1101/2023.05.25.542308.
Purkinje cell (PC) synapses onto cerebellar nuclei (CbN) neurons convey signals from the cerebellar cortex to the rest of the brain. PCs are inhibitory neurons that spontaneously fire at high rates, and many uniform sized PC inputs are thought to converge onto each CbN neuron to suppress or eliminate firing. Leading theories maintain that PCs encode information using either a rate code, or by synchrony and precise timing. Individual PCs are thought to have limited influence on CbN neuron firing. Here, we find that single PC to CbN synapses are highly variable in size, and using dynamic clamp and modelling we reveal that this has important implications for PC-CbN transmission. Individual PC inputs regulate both the rate and timing of CbN firing. Large PC inputs strongly influence CbN firing rates and transiently eliminate CbN firing for several milliseconds. Remarkably, the refractory period of PCs leads to a brief elevation of CbN firing prior to suppression. Thus, PC-CbN synapses are suited to concurrently convey rate codes, and generate precisely-timed responses in CbN neurons. Variable input sizes also elevate the baseline firing rates of CbN neurons by increasing the variability of the inhibitory conductance. Although this reduces the relative influence of PC synchrony on the firing rate of CbN neurons, synchrony can still have important consequences, because synchronizing even two large inputs can significantly increase CbN neuron firing. These findings may be generalized to other brain regions with highly variable sized synapses.
浦肯野细胞（PC）与小脑核（CbN）神经元之间的突触将信号从小脑皮质传递到大脑的其他部分。浦肯野细胞是抑制性神经元，会以高频率自发放电，许多大小一致的浦肯野细胞输入被认为会聚到每个小脑核神经元上，以抑制或消除放电。主流理论认为，浦肯野细胞要么使用频率编码，要么通过同步和精确计时来编码信息。单个浦肯野细胞被认为对小脑核神经元放电的影响有限。在这里，我们发现单个浦肯野细胞与小脑核之间的突触大小高度可变，并且通过动态钳制和建模，我们揭示了这对浦肯野细胞 - 小脑核的信号传递具有重要意义。单个浦肯野细胞输入调节小脑核放电的频率和时间。较大的浦肯野细胞输入强烈影响小脑核放电频率，并在几毫秒内短暂消除小脑核放电。值得注意的是，浦肯野细胞的不应期会导致在抑制之前小脑核放电短暂升高。因此，浦肯野细胞 - 小脑核突触适合同时传递频率编码，并在小脑核神经元中产生精确计时的反应。可变的输入大小还通过增加抑制性电导的变异性来提高小脑核神经元的基础放电频率。尽管这降低了浦肯野细胞同步对小脑核神经元放电频率的相对影响，但同步仍然可能产生重要影响，因为即使两个大输入同步也能显著增加小脑核神经元放电。这些发现可能适用于其他具有高度可变突触大小的脑区。
