Tsc1ΔE18/ΔE18 spikes Selumetinib cost did not differ significantly from those of Tsc1+/+ neurons in terms of amplitude, depolarization rate, or repolarization rate ( Figure S5). VB action potentials are typically followed by fast and slow afterhyperpolarizations (AHPs) and an afterdepolarization (ADP) of intermediate duration ( Figure 6D, black trace). To compare these events, we summed the total area under the postaction potential trajectory, which revealed that the Tsc1ΔE12/ΔE12 neurons had significantly more negative afterpotentials compared to controls

(−177 mV*ms versus −64 mV*ms, p = 0.0026; Figure 6D). The Tsc1ΔE18/ΔE18 afterpotentials did not differ significantly from controls ( Table S1). Thalamic relay neurons fire in both tonic and bursting modes, depending on the state of the resting membrane potential. We characterized tonic firing by holding the membrane potential at −50 mV and applying steps of depolarizing current. While the amplitudes of Tsc1+/+ action potentials declined over the first 100 ms of spiking (adaptation), the amplitudes

of Tsc1ΔE12/ΔE12 action potentials remained constant ( Figure 6E, arrows). The relationship between firing frequency and stimulus current was roughly linear for both Tsc1+/+ and Tsc1ΔE12/ΔE12 cells ( Figure 6F). The average slope of the frequency/current relationship for Tsc1ΔE12/ΔE12 cells (0.27 Hz/pA) was significantly lower than that of Tsc1+/+ cells from littermate controls (0.53 Hz/pA, p < 0.001, n ≥ 11 cells recorded from n ≥ 3 animals per group; Figure 6G). this website Frequency/current relationships of Tsc1ΔE18/ΔE18 cells did not differ from those of littermate controls ( Figures 6G and S5). We next characterized the cells’ burst firing by holding membrane potentials initially at −60 mV, then injecting a 1 s step of current sufficient to bring the membrane to −70 mV. Upon release of the current, VB neurons fired a single burst of spikes ( Figure 6H). Each burst comprised a similar number of action potentials

that did not vary by genotype; however, the mean duration of the Tsc1ΔE12/ΔE12 bursts were shorter. Figure 6I plots the intraburst frequency as a function of spike number within the bursts; Tsc1ΔE12/ΔE12 neurons had a significantly higher mean spiking frequency throughout unless the burst (401 Hz) compared to Tsc1+/+ littermate controls (mean of 339 Hz, p = 0.026). Tsc1ΔE18/ΔE18 neurons were not significantly different from neurons of Tsc1+/+ littermates ( Figures 6J and S5). These experiments revealed that the enlarged Tsc1ΔE12/ΔE12 neurons require stronger input currents to modify their membrane potentials, have larger, faster action potentials, and have altered firing properties in both tonic and bursting mode, compared to wild-type VB neurons, whereas Tsc1ΔE18/ΔE18 neurons were unaltered. To determine whether the changes in thalamic development and physiology impact neocortical physiology, we recorded local field potentials (LFPs) in the vibrissal representation of primary SI of adult anesthetized mice.