Figure 6.

Activation of hM4Di in spared dorsolaterally projecting corticospinal neurons abrogates spontaneous recovery on the horizontal ladder task after C3/C4 dorsal column SCI. A, Experimental schedule. AAV injections were made at 4 weeks after injury and DREADD receptor behavioral experiments at 55–58 d after injury by administering CNO on day 56 and 58. B, Timeline of left FL error percentage in injured and sham-operated mice with AAV1-hSyn-dio-hM4D(Gi)-mCherry + AAV1-iCre injections (hm4Di Cre+) or just AAV1-hSyn-dio-hM4D(Gi)-mCherry for control (hm4Di Cre−). HM4Di Cre− SCI mice have lower error percentage at 55–58 d after injury versus 7 d after injury. HM4Di Cre+ SCI mice have lower error percentage at 55 and 57 d after injury versus 7 d after injury, but not at 56 and 58 d after injury, the 2 d when CNO was administered. C, Left FL error percentages after vehicle administration and CNO administration for each group (calculated as an average of scores on 55 and 57 d and 56 and 58 d, respectively). HM4Di SCI Cre+ mice have a higher error percentage after CNO administration versus vehicle administration and versus sham hM4Di Cre+ mice after CNO administration. hM4DI sham-operated mice have a higher error percentage after CNO administration versus vehicle administration. D, Left FL delta error percentage calculated as the absolute difference between CNO error percentage and vehicle error percentage. hM4Di SCI Cre+ mice have a higher delta error percentage than hM4Di Sham Cre+ mice. E, Timeline of right FL error percentage in injured and sham-operated mice as in B. All four groups have a lower error percentage at 55–58 d after injury versus 7 d after injury. F, Right FL error percentages after vehicle administration and CNO administration for each group. hM4Di SCI Cre+ mice trend toward a higher error percentage after CNO administration versus vehicle administration (p = 0.06). G, Right FL delta error percentage. ***p < 0.001, **p < 0.01, *p < 0.05. Error bars indicate SEM.