Statistical mapping of sound-evoked activity in the mouse auditory midbrain using Mn-enhanced MRI

Abstract

Manganese-enhanced MRI (MEMRI) has been developed to image brain activity in small animals, including normal and genetically modified mice. Here, we report the use of a MEMRI-based statistical parametric mapping method to analyze sound-evoked activity in the mouse auditory midbrain, the inferior colliculus (IC). Acoustic stimuli with defined frequency and amplitude components were shown to activate and enhance neuronal ensembles in the IC. These IC activity patterns were analyzed quantitatively using voxel-based statistical comparisons between groups of mice with or without sound stimulation. Repetitive 40-kHz pure tone stimulation significantly enhanced ventral IC regions, which was confirmed in the statistical maps showing active regions whose volumes increased in direct proportion to the amplitude of the sound stimuli (65dB, 77dB, and 89dB peak sound pressure level). The peak values of the activity-dependent MEMRI signal enhancement also increased from 7 to 20% for the sound amplitudes employed. These results demonstrate that MEMRI statistical mapping can be used to analyze both the 3D spatial patterns and the magnitude of activity evoked by sound stimuli carrying different energy. This represents a significant advance in the development of MEMRI for quantitative and unbiased analysis of brain function in the deep brain nuclei of mice.

Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia

“…Therefore, to track brain activity in awake, freely moving animals, we used a modified MEMRI protocol that decouples isofluorane anesthesia and DOI administration. Previously, MEMRI was successfully applied to analyze cocaine-, sound-, and odor-induced activities (9,11,12,21), as well as brain plasticity in song birds (10). Because Mn 2+ can be neurotoxic (22,23), we carried out a pilot experiment on naive, 6-wk-old C57BL/6J mice to establish a protocol and study the effects of Mn 2+ on general animal health and DOI-induced behavior.…”

“…By taking advantage of the fact that Mn 2+ enters excitable cells via voltage-gated calcium channels, MEMRI has been used to study cocaine-induced neuronal activity (9), brain plasticity in song birds (10), and sound-evoked activity (11,12). The approach in the first two studies has some limitations, as it is invasive, whereas the latter study required exposure to a prolonged, repetitive stimulus.…”

“…4). For the analysis, we apply an MEMRIbased statistical parametric mapping (SPM) method that was successfully used to measure sound-induced activity in a quantitative and unbiased manner (9,12). We compare DOI-induced Mn 2+ uptake in MIA versus control offspring performing a 2 × 2 factorial analysis with drug (DOI or saline) and MIA [poly(I:C) or saline] treatments as the independent factors and the signal intensity difference before and after drug administration as the dependent factor.…”

Imaging neuronal pathways with 52Mn PET: Toxicity evaluation in rats

“…It is known that microtubules contribute to, although probably are not fully responsible for, the axonal transport of 54 Mn (Sloot and Gramsbergen, 1994) and the same mechanism would be expected for 52 Mn. Furthermore, studies utilizing non-radioactive Mn 2+ have shown that the transport, as well as the uptake, depend on neuronal activity, and that voltage-gated Ca and Na channels are involved in these processes (Lin and Koretsky, 1997, Yu et al, 2008, Wang et al, 2015.…”

Magnetic Resonance Microscopy

“…This technique was shown to identify activated regions of the rodent brain which "light-up" in T 1 -weighted images following auditory [117,118] or somatosensory stimulation [3,50,113], performed after injection manganese chloride [50]. However, the fact that this technique requires general anesthesia and opening of the blood brain barrier, as well as the toxicity of manganese, are issues that need to be considered [30] in order to fully exploit the potential of MEMRI for imaging plasticity, testing behavioral paradigms, or studying the effects of pharmacological agents or substances of abuse on the central nervous system [73].…”