Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Broad Institute of Harvard and MIT, Stanley Center for Psychiatric Research, 450 Main St., Cambridge, MA, USA.
Nat Commun. 2021 Oct 7;12(1):5491. doi: 10.1038/s41467-021-22893-8.
Many neuron types consist of populations with continuously varying molecular properties. Here, we show a continuum of postsynaptic molecular properties in three types of neurons and assess the functional correlates in cerebellar unipolar brush cells (UBCs). While UBCs are generally thought to form discrete functional subtypes, with mossy fiber (MF) activation increasing firing in ON-UBCs and suppressing firing in OFF-UBCs, recent work also points to a heterogeneity of response profiles. Indeed, we find a continuum of response profiles that reflect the graded and inversely correlated expression of excitatory mGluR1 and inhibitory mGluR2/3 pathways. MFs coactivate mGluR2/3 and mGluR1 in many UBCs, leading to sequential inhibition-excitation because mGluR2/3-currents are faster. Additionally, we show that DAG-kinase controls mGluR1 response duration, and that graded DAG kinase levels correlate with systematic variation of response duration over two orders of magnitude. These results demonstrate that continuous variations in metabotropic signaling can generate a stable cell-autonomous basis for temporal integration and learning over multiple time scales.
许多神经元类型由具有连续变化分子特性的群体组成。在这里，我们展示了三种神经元中连续的突触后分子特性，并评估了小脑单极刷状细胞 (UBC) 中的功能相关性。虽然 UBC 通常被认为形成离散的功能亚型，MF 激活增加 ON-UBC 的放电，抑制 OFF-UBC 的放电，但最近的工作也指出了反应谱的异质性。事实上，我们发现了一系列反映兴奋性 mGluR1 和抑制性 mGluR2/3 途径的渐变和反向相关表达的反应谱。MF 在许多 UBC 中共激活 mGluR2/3 和 mGluR1，导致顺序抑制-兴奋，因为 mGluR2/3 电流更快。此外，我们表明 DAG-激酶控制 mGluR1 反应持续时间，并且分级 DAG 激酶水平与反应持续时间在两个数量级上的系统变化相关。这些结果表明，代谢型信号转导的连续变化可以为跨多个时间尺度的时间整合和学习生成稳定的细胞自主基础。
