Najac Marion, Raman Indira M
Department of Neurobiology, Northwestern University, Evanston, Illinois 60208.
Department of Neurobiology, Northwestern University, Evanston, Illinois 60208
J Neurosci. 2015 Jan 14;35(2):544-9. doi: 10.1523/JNEUROSCI.3583-14.2015.
Neurons in the cerebellar cortex, cerebellar nuclei, and inferior olive (IO) form a trisynaptic loop critical for motor learning. IO neurons excite Purkinje cells via climbing fibers and depress their parallel fiber inputs. Purkinje cells inhibit diverse cells in the cerebellar nuclei, including small GABAergic nucleo-olivary neurons that project to the IO. To investigate how these neurons integrate synaptic signals from Purkinje cells, we retrogradely labeled nucleo-olivary cells in the contralateral interpositus and lateral nuclei with cholera toxin subunit B-Alexa Fluor 488 and recorded their electrophysiological properties in cerebellar slices from weanling mice. Nucleo-olivary cells fired action potentials over a relatively narrow dynamic range (maximal rate, ∼ 70 spikes/s), unlike large cells that project to premotor areas (maximal rate, ∼ 400 spikes/s). GABA(A) receptor-mediated IPSCs evoked by electrical or optogenetic stimulation of Purkinje cells were more than 10-fold slower in nucleo-olivary cells (decay time, ∼ 25 ms) than in large cells (∼ 2 ms), and repetitive stimulation at 20-150 Hz evoked greatly summating IPSCs. Nucleo-olivary firing rates varied inversely with IPSP frequency, and the timing of Purkinje IPSPs and nucleo-olivary spikes was uncorrelated. These attributes contrast with large cells, whose brief IPSCs and rapid firing rates can permit well timed postinhibitory spiking. Thus, the intrinsic and synaptic properties of these two projection neurons from the cerebellar nuclei tailor them for differential integration and transmission of their Purkinje cell input.
小脑皮质、小脑核团和下橄榄核（IO）中的神经元形成了一个对运动学习至关重要的三突触回路。IO神经元通过攀缘纤维兴奋浦肯野细胞，并抑制其平行纤维输入。浦肯野细胞抑制小脑核团中的多种细胞，包括投射到IO的小GABA能核橄榄神经元。为了研究这些神经元如何整合来自浦肯野细胞的突触信号，我们用霍乱毒素亚基B- Alexa Fluor 488逆行标记对侧间位核和外侧核中的核橄榄细胞，并在断奶小鼠的小脑切片中记录它们的电生理特性。与投射到运动前区的大细胞（最大放电频率约为400次/秒）不同，核橄榄细胞在相对较窄的动态范围内发放动作电位（最大频率约为70次/秒）。电刺激或光遗传学刺激浦肯野细胞诱发的GABA(A)受体介导的抑制性突触后电流（IPSCs）在核橄榄细胞中的衰减速度（衰减时间约为25毫秒）比在大细胞中（约为2毫秒）慢10倍以上，并且在20-150赫兹的重复刺激下诱发了强烈的IPSCs总和。核橄榄细胞的放电频率与抑制性突触后电位（IPSP）频率呈反比，并且浦肯野细胞IPSPs和核橄榄细胞动作电位的时间不相关。这些特性与大细胞形成对比，大细胞短暂的IPSCs和快速的放电频率可以实现适时的抑制后发放。因此，来自小脑核团的这两种投射神经元的内在和突触特性使它们能够对浦肯野细胞输入进行差异整合和传递。
