Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies
Section snippets
Methods
Male Sprague–Dawley rats (250–300 g) were used in the present study. Rats were maintained on a 12 h light/dark illumination cycle, housed in groups of four and had ad libitum access to food and water. All experimental procedures were approved by the local authorities (Regierungspraesidium) and were in full compliance with the guidelines of the European Communities Council Directive of 24 November 1986 (86/609/EEC) for the care and use of the laboratory animals.
Behavioral effects of a single systemic injection of MnCl2
The voluntary running activity in intact rats was progressively increasing over 6 days of testing from 131.1 ± 11.4 to 301.2 ± 42.7 (mean ± SE) meters per hour as revealed by repeated measures ANOVA (F2,34.5 = 13.1, p < 0.001; Supplementary Fig.1). The running activity did not depend on a particular time of day when the 3-h test was performed (F3.7,27.6 = 1.32, ns for test × time interaction). Due to substantial individual variability in voluntary running activity (e.g. min/max: 147.6/792.2 m per hour on
Discussion
The results of the present study convincingly demonstrate that continuous and slow administration of MnCl2 over prolonged period is advantageous for longitudinal behavioral studies compared to a single systemic injection of the same dose. The method described here allows avoiding toxic effects of manganese, while the latter reaches MRI-detectable cumulative amounts in the brain. Chronically implanted osmotic pumps are perfectly suited for such purpose. They provide a nicely controlled
Acknowledgments
This work was supported by Max-Planck Society (O.E.) and Human Frontier Science Program Organization (S.C.). We thank Dr. Helmut Merkle for construction of saddle RF coils.
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2020, NeuroImageCitation Excerpt :In this study, MEMRI with a protocol of 7-day continuous MnCl2 infusion was used to map accumulative brain activities in the EE-treated mice. Similar approaches have been used in previous studies to assess brain activations associated with voluntary wheel-running and alcohol/saccharin consumption (Dudek et al., 2015; Eschenko et al., 2010). With days of MnCl2 infusion, the amount of regional Mn2+ deposition not only reflects the integrated local neuronal activities over time (Bissig and Berkowitz, 2009; Lu et al., 2007; Yu et al., 2005), but also is modulated by factors such as axonal/trans-synaptic Mn2+ transport and changes in BBB permeability (Androuin et al., 2019; den Hollander et al., 2014; Eschenko et al., 2010).
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- 1
Authors contributed equally.
- 2
Current address: Instituto de Neurociencias, Campus de San Juan, 03550 San Juan de Alicante, Alicante, Spain.
- 3
Current address: Max Planck Institute for Psycholinguistics and Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.