Neuronal projections from ventral tegmental area to forebrain structures in rat studied by manganese-enhanced magnetic resonance imaging

Li, Yingxia; Fang, Fang; Wang, Xuxia; Lei, Hao

doi:10.1016/j.mri.2008.07.011

Cited by 12 publications

(6 citation statements)

References 41 publications

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“…The VTA is similarly involved in several higher order cognitive processes such as reward seeking and working memory (Carr et al, 1999; Chambers et al, 2010; Greene, 2006; Grimm et al, 2004; Li et al, 2009; Pang et al, 1993; Schultz, 1998; Vucetic et al, 2010; Wang et al, 2010). Previous accounts of the VTA projection system indicate that its efferents do not collateralize extensively (Loughlin and Fallon, 1984; Sobel and Corbett, 1984).…”

Section: Introductionmentioning

confidence: 99%

Identification and distribution of projections from monoaminergic and cholinergic nuclei to functionally differentiated subregions of prefrontal cortex

2013

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The prefrontal cortex (PFC) is implicated in a variety of cognitive and executive functions and is composed of several distinct networks, including anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). These regions serve dissociable cognitive functions, and are heavily innervated by acetylcholine, dopamine, serotonin and norepinephrine systems. In this study, fluorescently labeled retrograde tracers were injected into the ACC, mPFC, and OFC, and labeled cells were identified in the nucleus basalis (NB), ventral tegmental area (VTA), dorsal raphe nucleus (DRN) and locus coeruleus (LC). DRN and LC showed similar distributions of retrogradely labeled neurons such that most were single labeled and the largest population projected to mPFC. VTA showed a slightly greater proportion of double and triple labeled neurons, with the largest population projecting to OFC. NB, on the other hand, showed mostly double and triple labeled neurons projecting to multiple subregions. Therefore, subsets of VTA, DRN and LC neurons may be capable of modulating individual prefrontal subregions independently, whereas NB cells may exert a more unified influence on the three areas simultaneously. These findings emphasize the unique aspects of the cholinergic and monoaminergic projections to functionally and anatomically distinct subregions of PFC.

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Section: Introductionmentioning

confidence: 99%

Identification and distribution of projections from monoaminergic and cholinergic nuclei to functionally differentiated subregions of prefrontal cortex

2013

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“…A similar dose (45 nmol of Mn 2+ ) caused degeneration of the dopaminergic ventral tegmental area (VTA) neurons after a direct intracerebral injection in rats (own unpublished data). In another study, 40 nmol of Mn 2+ unilaterally injected into a rat VTA was found to significantly affect the cells morphology, and even the 20 nmol dose reduced the number of "normal-appearing neurons" (Li et al, 2009).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 92%

“…Currently, doses in the range of tens of nmol are typically used for tracing neuronal pathways with MEMRI (Saleem et al, 2002, Murayama et al, 2006, Li et al, 2009). However, it has been shown that 50 nmol of Mn 2+ injected into the vitreous body of a mouse eye disturbed neuronal electrophysiology measured in the visual cortex (Bearer et al, 2007).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

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

et al. 2017

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Manganese in its divalent state (Mn 2+ ) has features that make it a unique tool for tracing neuronal pathways. It is taken up and transported by neurons in an activity dependent manner and it can cross synapses. It also acts as a contrast agent for magnetic resonance imaging (MRI) enabling visualization of neuronal tracts. However, due to the limited sensitivity of MRI systems relatively high Mn 2+ doses are required. This is undesirable, especially in long-term studies, because of the known toxicity of the metal.In order to overcome this limitation, we propose 52 Mn as a positron emission tomography (PET) neuronal tract tracer. We used 52 Mn for imaging dopaminergic pathways after a unilateral injection into the ventral tegmental area (VTA), as well as the striatonigral pathway after an injection into the dorsal striatum (STR) in rats. Furthermore, we tested potentially noxious effects of the radioactivity dose with a behavioral test and histological staining. 24 h after 52 Mn administration, the neuronal tracts were clearly visible in PET images and statistical analysis confirmed the observed distribution of the tracer. We noticed a behavioral impairment in some animals treated with 170 kBq of 52 Mn, most likely caused by dysfunction of dopaminergic cells. Moreover, there was a substantial DNA damage in the brain tissue after applying 150 kBq of the tracer. However, all those effects were completely eliminated by reducing the 52 Mn dose to 20-30 kBq. Crucially, the reduced dose was still sufficient for PET imaging.

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“…Therefore, it more likely resulted from the manganese crossing BBB into the cerebrospinal fluid (CSF) or brain during BBB opening. Moreover, some previous studies have already showed the potential of manganese in CSF or brain transferring into the activated brain areas (Bearer et al 2007;Li et al 2009;Liu et al 2004). It could therefore be assumed that the temporary disruption of BBB would have a twofold effect that is as recognized allowing Mn 2+ to enter the activated brain areas more effectively during BBB opening, and as unconfirmed allowing Mn 2+ in the CSF or brain to sequentially transfer to the activated brain areas.…”

Section: Introductionmentioning

confidence: 99%

Effects of temporarily disrupting BBB on activity-induced manganese-dependent functional MRI

Zhang

et al. 2011

Brain Imaging and Behavior

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This study further investigates the influence of temporarily disrupting the blood-brain barrier (BBB) on the level of manganese used in AIM fMRI other than the recognized function of allowing that substance to enter into the activated brain regions more effectively during the BBB opening. We injected manganese into Wistar rats through ICA following the disruption of BBB with mannitol in a functional MRI test of the visual cortex. Through comparing MRI signal intensity and manganese contents in the visual cortex of rats received visual stimuli of unequal degree after the restoration of BBB, we found that the signal in the visual cortex could be further enhanced on T1WI given visual stimulation after the restoration of BBB. Temporary BBB disruption has an additional advantage in allowing Mn(2+) to enter the CSF or brain for later transference to the activated brain area. So the dosage of manganese in AIM fMRI could be minimized by extending the stimulus.

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Neuronal projections from ventral tegmental area to forebrain structures in rat studied by manganese-enhanced magnetic resonance imaging

Cited by 12 publications

References 41 publications

Identification and distribution of projections from monoaminergic and cholinergic nuclei to functionally differentiated subregions of prefrontal cortex

Identification and distribution of projections from monoaminergic and cholinergic nuclei to functionally differentiated subregions of prefrontal cortex

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

Effects of temporarily disrupting BBB on activity-induced manganese-dependent functional MRI

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