Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

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.

Spatial memory training induces morphological changes detected by manganese-enhanced MRI in the hippocampal CA3 mossy fiber terminal zone

“…Another study498 showed that the behavior and electrophysiology were not affected 499 at 0.1 mmol/kg of Mn 2+ but that the task latency was increased at 500 0.5 mmol/kg Mn 2+(Eschenko et al, 2010). In our study, 80 mg/kg 501 Mn 2+ was infused at 6 days after training on the water maze task.…”

Visualizing odor representation in the brain: a review of imaging techniques for the mapping of sensory activity in the olfactory glomeruli

“…Odor-induced activity recordings with functional MEMRI were first demonstrated by Pautler and Koretsky [102]. MEMRI signals in the MOB can be obtained either by intraperitoneal injection of manganese chloride (which might induce neurotoxicity [103]) or by nasal injection which is the preferred pathway to map the connectivity in the olfactory system. Recently, functional maps of odorant stimulation with individual glomerular spatial resolution were obtained [104].…”

Development of a MR-Visible Compound for Tracing Neuroanatomical Connections In Vivo

“…Additional complications arise from a non-neuronal systemic diffusion of manganese through the CSF or blood stream (Chuang and Koretsky, 2009). Also, manganese is toxic above a specific dose (Wu et al, 2006; Simmons et al, 2008; Eschenko et al, 2010a,b). …”