. 2021 May 19;15:665386. doi: 10.3389/fncir.2021.665386

TABLE 2.

Effect of toxins on DA neuron GLU cotransmission.

Species and Age	Genotype	Method	Toxin	TH⁺VGLUT2⁺/Total TH⁺%		Effect on DA neurons	Citation
				VTA	SN
Rat P15	WT	ISH	Vehicle	7.1	0.7	In NAc% TH⁺/VGLUT2⁺ axon terminals higher in 6-OHDA group (37.4%) vs. vehicle (28.2%)	Dal Bo et al., 2008
			6-OHDA Intraventricular on P4 (perfusion 11d later)	26	0.0
Mouse P52	WT	IHC	Vehicle	15	9.0	Increased loss of SN TH⁺ neurons	Steinkellner et al., 2018
			6-OHDA Dorsal striatum on P42 (perfusion 10d later)	19	21
	DAT^IRES–Cre/+; VGluT2^flox/+ or DAT^IRES–Cre/+; VGluT2^flox/flox	IHC	6-OHDA Dorsal striatum on P42 (perfusion 10d later)	−		Increased loss of SN TH⁺ neurons, significantly more in cKO mice
Mouse P8–12 weeks	DAT^IRES–Cre/+; VGluT2^flox/+ or DAT^IRES–Cre/+; VGluT2^flox/flox	IHC	Acute MPTP 15 mg/kg i.p. × 4 2 h apart, same day. (perfusion 7 h later)	−		Increased loss of midbrain TH⁺ neurons in cKO mice
			Chronic MPTP 30 mg/kg i.p. × 5 days (perfusion 21 days later)	−		Increased loss of midbrain TH⁺ neurons in cKO mice
Mouse P8–12 weeks	DAT^IRES–Cre/+; VGluT2^flox/+	IHC	Vehicle	15	20	Increased loss of VTA and SN TH⁺ neurons in cKO mice. Reduced TH and DAT throughout striatum. Viral rescue of VGluT2 in DA neurons slightly attenuated reduction	Shen et al., 2018
			Acute MPTP 18 mg/kg; i.p. × 4 2 h apart, same day. (perfusion 14 days later)	35	45
	DAT^IRES–Cre/+; VGluT2^flox/flox		Acute MPTP 18 mg/kg; i.p. × 4 2 h apart, same day. (perfusion 14 days later)	–	–
Mouse > P60	DAT^IRES–Cre/+; VGluT2^flox/flox		Acute 6-OHDA Dorsal striatum (perfusion 7 weeks later)	-	-	Impaired striatal re-innervation post-6-OHDA in cKO mice.	Kouwenhoven et al., 2020
Rat P90	WT	ISH	Artificial cerebrospinal fluid	2.4	0.3	In NAc% of TH⁺/VGLUT2⁺ axon terminals higher with 6-OHDA (0.05%) vs. vehicle (0%)	Bérubé-Carrière et al., 2009
			6-OHDA Intraventricular on P4 (perfusion 11 days later)	7.2	0.0