Improved neuronal tract tracing with stable biocytin-derived neuroimaging agents.
One of the main characteristics of brains is their profuse connectivity at different spatial scales. Understanding brain function evidently first requires a comprehensive description of neuronal anatomical connections. Not surprisingly a large number of histological markers were developed over the years that can be used for tracing mono- or polysynaptic connections. Biocytin is a classical neuroanatomical tracer commonly used to map brain connectivity. However, the endogenous degradation of the molecule by the action of biotinidase enzymes precludes its applicability in long-term experiments and limits the quality and completeness of the rendered connections. With the aim to improve the stability of this classical tracer, two novel biocytin-derived compounds were designed and synthesized. Here we present their greatly improved stability in biological tissue along with retained capacity to function as neuronal tracers. The experiments, 24 and 96 h postinjection, demonstrated that the newly synthesized molecules yielded more detailed and complete information about brain networks than that obtained with conventional biocytin. Preliminary results suggest that the reported molecular designs can be further diversified for use as multimodal tracers in combined MRI and optical or electron microscopy experiments.
Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tübingen 72076, Germany.
Anurag
A
Mishra
Kirti
K
Dhingra
Almut
A
Schüz
Nikos K
NK
Logothetis
Santiago
S
Canals
D000818:Animals; D043523:Biotinidase / Q000737:chemistry; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000033:anatomy & histology; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents; D007202:Indicators and Reagents; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D009434:Neural Pathways / Q000033:anatomy & histology*; D059906:Neuroimaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013534:Survival
D004396:Coloring Agents; D007202:Indicators and Reagents; D043523:Biotinidase; C013411:biocytin; D008239:Lysine