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

Zhang, Binbin; Chuang, Kai‐Hsiang; Tjio, Ci'en; Chen, Way Cherng; Sheu, Fwu‐Shan; Routtenberg, Aryeh

doi:10.1016/j.neuroimage.2015.07.084

Cited by 7 publications

(9 citation statements)

References 62 publications

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“…For instance, in vivo MEMRI was used to show that hippocampal volume changes during the mouse estrus cycle, and that this influences spatial learning [24]. MEMRI has also been used to monitor hippocampal plasticity in response to spatial learning and environmental enrichment [22,23]. While these studies delivered MnCl 2 via intraperitoneal injection, continuous delivery of MnCl 2 via osmotic pumps is increasingly being used to bypass adverse side effects when when a high cumulative dose of Mn 2+ is required [33,32,12,34].…”

Section: Use Of Memri In Studies Of Learning and Memorymentioning

confidence: 99%

“…Based on our study, delivery of 25 mg/kg/day of MnCl 2 is best suited to studies where mice are imaged at several time points over a ∼10 day window. For instance, this approach could be used for short term studies of plasticity [22] but is ill-suited for long term imaging designs [23]. In our view, studies with single imaging points and longer-term studies with less frequent imaging time-points are better performed using systemic injections of MnCl 2 .…”

Section: 4mentioning

confidence: 99%

“…The uptake of Mn 2+ provides excellent visualization of cytoarchitecture [1]. Given this, MEMRI has many applications, including functional imaging of brain regions involved in specific behaviours [11,12], neuronal tract tracing [13,14,15,16,17,18], and imaging morphological changes through development [19], disease [20,21], or during behavioural paradigms [22,23,24].…”

Section: Introductionmentioning

confidence: 99%

“…One exciting potential application of longitudinal MEMRI studies is to monitor changes in functional activity or brain structure over time as animals learn a behavioural task [24,22,23]. A concern, though, is that Mn 2+ will impair function in the brain areas in which it accumulates in high amounts, such as the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

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Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

et al. 2018

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Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique in rodent neuroimaging studies. Traditionally, Mn is delivered to animals via a systemic injection; however, this can lead to toxic effects at high doses. Recent studies have shown that subcutaneously implanted mini-osmotic pumps can be used to continuously deliver manganese chloride (MnCl), and that they produce satisfactory contrast while circumventing many of the toxic side effects. However, neither the time-course of signal enhancement nor the effect of continuous Mn delivery on behaviour, particularly learning and memory, have been well-characterized. Here, we investigated the effect of MnCl dose and route of administration on a) spatial learning in the Morris Water Maze and b) tissue signal enhancement in the mouse brain. Even as early as 3 days after pump implantation, infusion of 25-50 mg/kg/day MnCl via osmotic pump produced signal enhancement as good as or better than that achieved 24 h after a single 50 mg/kg intraperitoneal injection. Neither route of delivery nor MnCl dose adversely affected spatial learning and memory on the water maze. However, especially at higher doses, mice receiving MnCl via osmotic pumps developed skin ulceration which limited the imaging window. With these findings, we provide recommendations for route and dose of MnCl to use for different study designs.

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Section: Use Of Memri In Studies Of Learning and Memorymentioning

confidence: 99%

Section: 4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

et al. 2018

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“…An increase in MEMRI signal intensity in the pyramidal cell layer of the CA1 is also observed in 6- to 18-month-old rats ( Bissig and Berkowitz, 2014 ). However, it is unclear if the changes represent accumulation in active neurons, active synapses, or glial cells ( Nairismagi et al, 2006 ; Hsu et al, 2007 ; Immonen et al, 2008 ; Eschenko et al, 2010 ; Perez et al, 2013 ; Zhang et al, 2015 ). For example, an increase in Mn 2+ signal intensity in dorsal CA1 and dentate gyrus of mice showing neurodegeneration and forebrain atrophy might be associated with increased presence of glial cells in the region ( Perez et al, 2013 ) and an increase in the area of Mn 2+ intensity was observed at the mossy fiber to CA3 synaptic terminal region following a learning ( Zhang et al, 2015 ).…”

Section: In Vivo Hippocampal and Cortical Volumetric Changesmentioning

confidence: 99%

Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

Febo

Foster

2016

Front. Aging Neurosci.

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Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline.

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Morris water maze overtraining increases the density of thorny excrescences in the basal dendrites of CA3 pyramidal neurons

Gómez-Padilla

Bello-Medina

León-Jacinto

et al. 2020

Behavioural Brain Research

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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

Cited by 7 publications

References 62 publications

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

Morris water maze overtraining increases the density of thorny excrescences in the basal dendrites of CA3 pyramidal neurons

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