Figure 2. SK Deficiency in nRT Neurons Underlies Intra-thalamic Circuit Hyperexcit-ability in DS Mice.

(A) Representative evoked intra-thalamic circuit oscillations in thalamic slices from WT and DS mice. Black circles indicate stimulation artifact. Left and right boxes indicate sections of the recording that were expanded, bottom left and right, respectively. Double-sided arrow indicates the length of the evoked oscillation in DS recording. Top right inset: schematic of the intrathalamic oscillatory microcircuit between VB and nRT. Stimulation of the internal capsule (black circle and lightning bolt) leads to an interplay of activity between nRT and TC_VB cells that resembles a ping-pong game causing a circuit oscillation whose strength can be assessed by VB recordings in horizontal thalamic slice preparations (see also Figure S6F).

(B–D) Data analyzed by the Mann-Whitney U test,WT, n = 9 mice; DS, n = 12 mice. Data are represented as means ± SEMs.

(B) Duration of evoked oscillation, **p < 0.01.

(C) Number of bursts within the evoked oscillation, *p < 0.05.

(D) Burst frequency within the evoked oscillation, **p < 0.01.

(E) Schematic of the full nRT-TC_VB circuit used for the computational modeling of thalamic oscillations in WT and DS conditions.

(F) Top: representative nRT and TC_VB voltage traces triggered by a stimulus (*) mimicking the electrical stimulation of the internal capsule, in the WT and DS conditions. Bottom: probability distributions of the duration of oscillations in the circuit over 1,000 simulations with different realizations of the stochastic current. The mean oscillation duration in the nRT-TC_VB circuit model in the DS condition is ~5 times that in the WT condition. The maximal conductances are as in Figure 1N.

(G, I, and K) Maps of the duration (G), burst number(I), and frequency (K) in the nRT-TC_VB circuit model, as a function of CaT and SK maximal conductances, computed over 30 simulations with different realizations of noise. The mean of these averages in the WT and DS domains (white and red boundaries, respectively) are indicated.(H, J, and L) Plots of means ± SEMs of the duration(H), burst number (J), and frequency (L) using 9 samples with randomly maximal conductances drawn from the WT domain and 12 samples with randomly maximal conductances drawn from the DS domain, with groups compared using the Mann-Whitney U test (H, **p = 0.0062; J, *p = 0.0208; L, **p = 0.0002).