Constitutive inhibition of neprilysin expression in DPM neurons induces MTM deficits. A, Flies expressing RNAi-Nep under the control of the constitutive MB-Gal80;c316 driver exhibit significantly lower MTM scores than the genetic controls (Nep1A: F(2,31) = 11.73, p = 0.0002, n ≥ 8, post hoc Newman–Keuls test, MB-Gal80;c316/Nep1A vs MB-Gal80;c316/+ **p < 0.01, MB-Gal80;c316/Nep1A vs +/Nep1A ***p < 0.001; Nep2A: F(2,31) = 10.72, p = 0.0003, n ≥ 8, post hoc Newman–Keuls test, MB-Gal80;c316/Nep2A vs MB-Gal80;c316/+ **p < 0.01, MB-Gal80;c316/Nep2A vs +/Nep2A ***p < 0.001; Nep3A: F(2,47) = 18.58, p < 0.0001, n = 16, post hoc Newman–Keuls test, MB-Gal80;c316/Nep3A vs MB-Gal80;c316/+ ***p < 0.001, MB-Gal80;c316/Nep3A vs +/Nep3A ***p < 0.001; Nep4A: F(2,46) = 6.939, p = 0.0024, n ≥ 15, post hoc Newman–Keuls test, MB-Gal80;c316/Nep4A vs MB-Gal80;c316/+ **p < 0.01, MB-Gal80;c316/Nep4A vs +/Nep4A **p < 0.01). B, Neprilysin inhibition in DPM neurons impairs MTM. VT64246/Nep1A, /Nep2A, /Nep3A, and /Nep4A flies exhibit MTM deficits compared with the genetic controls (Nep1A: F(2,30) = 7.403, p = 0.0026, n ≥ 9, post hoc Newman–Keuls test, VT64246/Nep1A vs VT64246/+ **p < 0.01, VT64246/Nep1A vs +/Nep1A **p < 0.01; Nep2A: F(2,29) = 7.942, p = 0.0019, n ≥ 8, post hoc Newman–Keuls test, VT64246/Nep2A vs VT64246/+ **p < 0.01, VT64246/Nep2A vs +/Nep2A **p < 0.01; Nep3A: F(2,41) = 21.33, p < 0.0001, n = 14, post hoc Newman–Keuls test, VT64246/Nep3A vs VT64246/+ ***p < 0.001, VT64246/Nep3A vs +/Nep3A ***p < 0.001; Nep4A: F(2,49) = 3.872, p = 0.0278, n ≥ 16, post hoc Newman–Keuls test, VT64246/Nep4A vs VT64246/+ *p < 0.05, VT64246/Nep4A vs +/Nep4A *p < 0.05).