Figure 7. DREADD-based activation of Pitx2⁺ interneurons increases motoneuron firing via M2 receptors and Kv2.1 channels.

(a) Spontaneous firing of a Pitx2⁺ interneuron from a Pitx2::Cre;tdTomato;hM3Dq mouse in control conditions and during the application of CNO; along with firing frequency data pooled for all recordings (n = 8). (b) Representative traces illustrating changes in holding current (Vhold = −60 mV) during recordings of motoneurons in the presence of CNO alone (left) or co-applied with methoctramine (10 μM, middle) or guangxitoxin-1E (50 nM, right). (c) Motoneuron firing in response to current steps in control conditions and in the presence of CNO (left) with pooled data plotted to show changes in rheobase, depolarizing block, current-frequency relationships and maximum firing (right) (n = 23). (d, e) Examples of motoneuron firing and pooled data depicting firing parameters in the presence of methoctramine and methoctramine co-applied with CNO (d; n = 11) or Guangxitoxin-1E and CNO co-applied with Guangxitoxin-1E (e; n = 14). *p>0.05, **p<0.01, ***p<0.001.

Figure 7—figure supplement 1. CNO has no effect on motoneuron properties in hM3Dq mice.

(a) CNO does not effect motoneuron firing parameters (rheobase, depolarizing block, current-frequency relationships or maximum firing rates, n = 15) and (b) mAHP amplitude (n = 4) in mice that do not express DREADD receptors. Input resistance also did not change in the presence of CNO (control: 77 ± 12 MΩ, CNO: 78 ± 12 MΩ, t(9)=0.499, Paired t-test, p=0.6295).