Figure 9.

The hypoactivity of putative PV^– GPe neurons in Q175 mice is alleviated by optogenetic inhibition of hyperactive PV⁺ GPe neurons. A, Representative examples of concurrent EEG (bandpass-filtered at 0.1-1.5 Hz) and GPe neuronal activity in Q175/WT X PV-cre mice during optogenetic inhibition (yellow bar) of PV⁺ GPe neurons. A–C, Optogenetic inhibition of PV⁺ GPe neuron activity rapidly and persistently disinhibited putative PV^– GPe neurons in Q175 and WT mice. B, C, PSTHs of putative PV^– GPe neuron activity in the absence and presence of PV⁺ GPe neuron optogenetic inhibition (yellow bar) (bin size, 100 ms; prestimulus mean, solid red line; ±2 SDs of prestimulus mean, dotted red line; B, PSTHs from representative neurons in A; C, population PSTHs). A–F, During cortical SWA, putative PV^– GPe neurons were less active than PV⁺ GPe neurons in both WT and Q175 mice. Furthermore, the frequency of putative PV^– GPe neuron activity in Q175 mice was lower than in WT mice (A, representative examples; D, population data). E, The precision of PV^– GPe neuron activity was similar in WT and Q175 mice. Optogenetic inhibition of PV⁺ GPe neurons disinhibited putative PV^– GPe neurons in WT and Q175 mice and eliminated the difference in firing frequencies between the two genotypes, arguing that GABAergic inhibition emanating from abnormally hyperactive PV⁺ GPe neurons is responsible for the relative hypoactivity of PV^– GPe neurons in Q175 mice (A, examples; F, population data). G, H, Relative to cortical SWA, there were no differences in the phase of putative PV^– GPe neuron activity in WT and Q175 mice, with or without optogenetic inhibition of PV⁺ GPe neurons. *p < 0.05.