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Updated: Jun 16, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI
Oxana Eschenko1, Santiago Canals, Irina Simanova
1Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tübingen, Germany.
Abstract:
Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn(2+) is a metabolic toxin and a competitive inhibitor for Ca(2+), and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl(2) administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl(2), respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl(2) dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca(2+) competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl(2). Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl(2) may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn(2+) administration protocol.
Insights
Manganese (Mn(2+))-enhanced MRI (MEMRI) can map brain activity, but Mn(2+) toxicity is a concern. Studies show low Mn(2+) doses (0.1 mmol/kg) are safe for cognitive network research, but higher doses (0.5 mmol/kg) impair response latency without causing histopathological damage.
Area of Science:
- Neuroscience
- Biophysics
- Pharmacology
Background:
- Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) enables longitudinal brain activity mapping in behaving animals.
- A key concern is whether Mn(2+) concentrations used in MEMRI may induce metabolic toxicity or interfere with Ca(2+) signaling, potentially altering brain physiology.
Purpose of the Study:
- To investigate the behavioral, electrophysiological, and histopathological effects of MnCl(2) administration at doses commonly employed in MEMRI studies.
- To determine the safety and potential physiological impact of Mn(2+) used for in vivo brain imaging.
Main Methods:
- Three groups of animals received subcutaneous injections of saline, 0.1 mmol/kg MnCl(2), or 0.5 mmol/kg MnCl(2).
- In vivo electrophysiological recordings in the hippocampal formation assessed excitatory postsynaptic potentials (EPSP) and population spikes (PS).
- Pair pulse facilitation and long-term potentiation (LTP) experiments evaluated synaptic function, alongside behavioral testing on a hippocampal-dependent learning task and immunohistological examination.
Main Results:
- The highest MnCl(2) dose (0.5 mmol/kg) caused a mild decrease in EPSP and PS amplitude, with preserved EPSP/PS ratio, suggesting presynaptic Ca(2+) competition rather than altered neuronal excitability.
- Synaptic plasticity (LTP) was unaffected by MnCl(2) treatment.
- Behaviorally, choice accuracy remained intact, but response latency significantly increased at the 0.5 mmol/kg MnCl(2) dose. No signs of neuronal toxicity or glial reaction were observed histologically.
Conclusions:
- MEMRI using 0.1 mmol/kg MnCl(2) appears safe for studying cognitive networks.
- Higher Mn(2+) doses (0.5 mmol/kg) can impact neuronal response latency and presynaptic function, necessitating careful consideration of dosage and protocol.
- Thorough toxicity assessment is crucial for each specific MEMRI study and Mn(2+) administration regimen.
