Figure 9. Comparisons between cortically-evoked spike characteristics of antidromically-identified striatonigral projection neurons recorded from DA depleted rAAV-naïve rats treated with chronic L-DOPA (LID+), rAAV-GFP injected L-DOPA naïve animals, or rAAV-Nurr1 injected L-DOPA naïve animals. A–C, Lesion status was confirmed with IHC for TH. TH immunoreactivity was dramatically reduced in the interjected hemisphere of the striatum (A) and substantia nigra (B). Stereological estimates of remaining TH-positive neurons show significant cell loss in both vector groups (C). D, E, Transgene expression from viral vector delivery was confirmed in the striatum with IHC for Nurr1 (D) or GFP (E). Scale bars: A, B, 1 mm; D, E 1 µm. F–J, Comparisons between cortically-evoked spike characteristics of antidromically-activated striatonigral projection neurons recorded from DA-depleted rAAV-naive rats treated with chronic l-DOPA (LID+), rAAV-GFP injected l-DOPA naive animals, or rAAV-Nurr1 injected l-DOPA naive animals. F, Traces of typical cortically-evoked responses from isolated striatonigral projection neurons. Ten consecutive overlaid responses are shown. Graphs compare the spike probability (G), average number of total spikes evoked during a stimulus trial at each current intensity tested (H), and onset latency of cortically-evoked spikes, in antidromically-identified dMSNs during cortical stimulation (I). Main stimulus intensity-dependent effects on cortically-evoked spike probability of dMSNs (striatonigral projection neurons) were observed in both LID+ and Nurr-1 overexpressing rats compared with vehicle treated DA-depleted GFP-expressing controls (*p< 0.001). Post hoc comparisons revealed a significant increase in the probability and number of evoked responses to cortical stimulation at the 400–600 µA current intensities in both LID+ and Nurr-1 overexpressing rats compared with vehicle treated DA-depleted, GFP-expressing control rats (*p< 0.05). No significant differences in onset latency (p> 0.05) or SD of latency (data not shown) of cortically-evoked responses were observed. J, The current threshold for eliciting antidromic spike activity in identified striatonigral dMSNs, which were not responsive to cortical stimulation recorded in rAAV-Nurr1 rats (242 µA ± 36.9) was significantly lower than that of vector naive, LID+ rats (608.9 µA ± 72.9, p = 0.0039), indicating that Nurr1 overexpression leads to an l-DOPA-independent upregulation in the axonal/terminal excitability of dMSNs that is greater than that induced by chronic l-DOPA exposure. Data are derived from N = 9/6 D1+ Nurr1- DA-depleted cells/rats (saline + l-DOPA; 5 mg/kg chronic, same acute challenge dose on the recording day), and N = 5/4 Nurr1+ DA-depleted cells/rats (saline + l-DOPA; 5 mg/kg acute challenge). **p = 0.0039.