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. 2018 Apr 25;23(4):951–958. doi: 10.1016/j.celrep.2018.03.111

Figure 3.

Figure 3

Intrinsic Properties and Subtypes of Human Layer 1 Interneurons

(A) Responses of example human (green) and mouse (red) L1-IN to current injections of −100, +25, and +75 pA (inset).

(B) Human neurons fired at higher frequencies across the entire range of injected currents (p < 0.001 for all current amplitudes, Kruskal-Wallis test, n = 46 human neurons and n = 66 mouse neurons).

(C) While the resting membrane potential of human and mouse L1-INs was similar (Vrest, −65.2 ± 0.7 versus −66.4 ± 0.8 mV, Kruskal-Wallis test, p = 0.28), human neurons displayed higher input resistance (286.0 ± 14.9 versus 208.4 ± 8.9 MΩ, Kruskal-Wallis test, p < 0.001) and lower action potential threshold compared to mice (−40.4 ± 0.5 versus −36.4 ± 0.7 mV, Kruskal-Wallis test, p < 0.001), with both factors likely contributing to the greater excitability of human L1-INs.

(D) These parameters showed no correlation with the disease history of the patients (p > 0.2, see also Figure S4).

(E) (left) Unsupervised hierarchical clustering on a set of active and passive physiological properties (Ward’s method on normalized datasets without prior assumption on cluster number) yielded a non-late-spiking and a late-spiking cluster in the mouse, which also differ in most other parameters (table presents mean, SEM and results of Kruskal-Wallis test). In addition to differences in spiking accommodation, voltage sag, and action potential afterhyperpolarization (Chu et al., 2003, Tasic et al., 2016, Jiang et al., 2013, Jiang et al., 2015), the late-spiking L1-INs display more depolarized action potential threshold, faster membrane time constant and lower action potential amplitude. (Right) The same unbiased analysis on human L1-INs yielded similar clusters, with a population of late-spiking cells that display smaller voltage sag, more depolarized action potential threshold, and faster membrane time constant. In addition, input resistance and resting membrane potential displayed similar trends in both species, whereas spiking accommodation, action potential afterhyperpolarization, and amplitude varied in a distinct manner between the two clusters in mouse and human. Calibration bar indicates value rank between 0 and 1.

(F) Example firing patterns. Error bars indicate SEM.

See also Figures S4 and S5.