1 APP+, a Fluorescent Analogue of the Neurotoxin MPP+, Is a Marker 2 of Catecholamine Neurons in Brain Tissue, but Not a Fluorescent 3 False Neurotransmitter

10 ABSTRACT: We have previously introduced fluorescent false 11 neurotransmitters (FFNs) as optical reporters that enable 12 visualization of individual dopaminergic presynaptic terminals 13 and their activity in the brain. In this context, we examined the 14 fluorescent pyridinium dye 4-(4-dimethylamino)phenyl-1-15 methylpyridinium (APP+), a fluorescent analogue of the 16 dopaminergic neurotoxin MPP+, in acute mouse brain tissue. 17 APP+ is a substrate for the dopamine transporter (DAT), 18 norepinephrine transporter (NET), and serotonin transporter 19 (SERT), and as such represented a candidate for the 20 development of new FFN probes. Here we report that APP 21 + labels cell bodies of catecholaminergic neurons in the 22 midbrain in a DAT- and NET-dependent manner, as well as fine dopaminergic axonal processes in the dorsal striatum. APP+ 23 destaining from presynaptic terminals in the dorsal striatum was also examined under the conditions inducing depolarization and 24 exocytotic neurotransmitter release. Application of a high concentration of KCl led to a small but significant degree of destainin