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. 2020 Mar 16;45(7):1159–1170. doi: 10.1038/s41386-020-0656-5

Fig. 2. Excessive GABA release from INs and decreased intrinsic excitability of PNs in the BTBR synapses.

Fig. 2

a, b IPSCs recorded in the whole-cell mode at a holding potential of −60 mV from PNs of WT (a) and BTBR (b) mice in NBQX (10 μM) and APV (50 μM) to block excitatory inputs. The same PNs were then exposed to TTX (1 μM) or bicuculline (10 μM). c, d Summary of the amplitude (c) and frequency (d) of IPSCs for WT (black bars) and BTBR (blue bars) PNs before (n = 16 for WT and BTBR) and after TTX exposure (n = 13 for WT; n = 9 for BTBR). The frequency is calculated as the reciprocal of each inter-IPSC-intervals and averaged for each neuron. e APs evoked by current steps (top) from a WT (middle) or BTBR (bottom) PN. All synaptic inputs are blocked by NBQX (10 μM), APV (50 μM) and bicuculline (10 μM). f, g Steady-state potentials (f) measured within last 5 ms of each evoked potential and number of spikes (g) generated by the current steps in WT (n = 10, black) and BTBR (n = 10, blue) neurons. Solid lines represent fits to a single exponential function: f(t) = Ae−t/τ +C (f) or a Boltzmann function: f(I) = Vmax/(1 + e(Imid-I)/Ic)+C (g). “Vmax” is theoretical value of the maximal number of APs; “Imid” is depolarization current needed to produce half of the maximal number of APs; “Ic” is steepness of the Boltzmann curve. h, i Summary of FO (h) and FSS (i) for WT (n = 10, black) and BTBR (n = 10, blue) PNs. FO and FSS are derived from the first and last inter-spike intervals, respectively (e). (j) Overlay of first spikes from a WT (black) and a BTBR (blue) PN, evoked by a current step of 1.1 nA. k, l Phase plane plots of the first spikes from WT (k) and BTBR (l) cells. m, n Maximal value of dV/dt (dV/dt Max, m) and spike threshold, i.e., the voltage where dV/dt reaches 5% of its maximum (n) are summarized for WT (n = 10, black bars) and BTBR (n = 10, blue bars) groups.