Fig. 7: The membrane potential and excitability of MC neurons are under control of glutamate-GABA interplay and tunable by MCS in acute mouse brain slices. | npj Parkinson's Disease

Fig. 7: The membrane potential and excitability of MC neurons are under control of glutamate-GABA interplay and tunable by MCS in acute mouse brain slices.

From: Motor cortex stimulation ameliorates parkinsonian locomotor deficits: effectual and mechanistic differences from subthalamic modulation

Fig. 7

a The membrane potential of MC PN is tunable by extracellularly-applied constant currents (MCS). Synaptic transmission is inhibited by CNQX, D-AP5, bicuculline, and CGP-35348. The voltage changes (∆V) are proportional to the hyperpolarizing (positive) MCS amplitude and the distance from the stimulating electrode (n = 3–11, wild-type or Thy1-ChR2-eYFP mice). b Selective photoexcitation (1.7 mW, 20 Hz, 300 ms, blue) of MC triggers glutamate release and elicits PN discharges according to the membrane potential (Vm) adjusted by MCS (n = 7, Thy1-ChR2-eYFP mice). c Electrical and optogenetic excitatory stimulation on MC (pulsatile, 20 Hz) similarly elicits EPSPs and putatively GABA-mediated responses (reversed at ~-65 mV) in the same PN. The change in baseline membrane potential (∆V) measured at 100 ms after light application is plotted against Vm before light (right, n = 11, Thy1-ChR2-eYFP mice). The line is a linear regression. d The responses of a representative PN to electrical stimulation on MC (20 Hz at different intensities) are altered by CNQX and bicuculline. e Selective photoexcitation (as that in b) induces GABA- and glutamate-dependent burst discharges in PN, where Vm is set at −70 mV by MCS (n = 11 bursts from 3 neurons). Burst duration is measured as the time interval between the first and the last spikes. f, g Paired recording of PN and IN shows that both neurons respond to excitatory inputs from MC (induced by optogenetic (f) or electrical (g) stimulation, see c) but PN is under more prominent GABAergic control. h Left, Hyperpolarizing MCS may increase the fidelity of PN relay (postsynaptic spike number/15 light pulses applied at 50 Hz on MC). Right, The fidelity of response (postsynaptic spike number/6 light pulses applied at 20 Hz on MC) is more decreased in IN than PN at a hyperpolarized membrane potential. Each n = 6 from Thy1-ChR2-eYFP mice. The drug concentration used: 10 μM CNQX, 20 μM D-AP5, 20 μM bicuculline, and 20 μM CGP-35348.

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