Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI

Shah, Disha; Blockx, Ines; Guns, Pieter-Jan; Deyn, Peter Paul De; Dam, Debby Van; Jonckers, Elisabeth; Palacios, Rafael Delgado y; Verhoye, Marleen; Linden, Annemie Van der

doi:10.1016/j.neuroimage.2015.01.009

Cited by 31 publications

(28 citation statements)

References 66 publications

(78 reference statements)

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“…The involvement of the DMN in cognitive processes might be mediated through, among others, the mAChR, so disruptions of this receptor subtype might result in disruptions of DMN FC and cognitive functions, as occur in Alzheimer's disease (Sheline and Raichle 2013). Consistent with that notion, a previous study shows how mAChR modulation results in FC deficits in defaultmode-like key regions and that these FC deficits are related to cognitive disruptions (Shah et al 2015). Moreover, functional MRI studies in human subjects showed that scopolamine induced altered activity (Sperling et al 2002;Antonova et al 2011) in DMN regions.…”

Section: Discussionmentioning

confidence: 59%

“…functional networks, studies in healthy rodents and rodent models of human neurological disorders might offer more flexibility to investigate the effect of specific modulations on the functional organization of the brain. For example, our recent study showed how modulating the cholinergic system with a muscarinic cholinergic receptor (mAChR) antagonist and agonist affects specific memory-related functional connections in the mouse brain, e.g., FC between the hippocampus and thalamus, between the cingulate and retrosplenial cortex, and between the visual and retrosplenial cortex (Shah et al 2015). These FC alterations could be linked to changes in memory performance, consistent with the known involvement of mAChRs in cognitive processes.…”

Section: Introductionmentioning

confidence: 63%

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Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain

et al. 2015

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Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 63%

Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain

et al. 2015

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“…Here, the fact that we did not identify connectivity differences in the non-PF group between the post-pre scans, suggests a satisfactory baseline assessment for the PF group. Other fMRI studies, however, show that scopolamine affects functional connectivity 88–91 . In light of the different scanning setup, different dosage and administration type, it seems that results are not conclusive as to the exact affected regions.…”

Section: Discussionmentioning

confidence: 95%

Intrinsic functional connectivity reduces after first-time exposure to short-term gravitational alterations induced by parabolic flight

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Wuyts

Jeurissen

et al. 2017

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Spaceflight severely impacts the human body. However, little is known about how gravity and gravitational alterations affect the human brain. Here, we aimed at measuring the effects of acute exposure to gravity transitions. We exposed 28 naïve participants to repetitive alterations between normal, hyper- and microgravity induced by a parabolic flight (PF) and measured functional MRI connectivity changes. Scans were acquired before and after the PF. To mitigate motion sickness, PF participants received scopolamine prior to PF. To account for the scopolamine effects, 12 non-PF controls were scanned prior to and after scopolamine injection. Changes in functional connectivity were explored with the Intrinsic Connectivity Contrast (ICC). Seed-based analysis on the regions exhibiting localized changes was subsequently performed to understand the networks associated with the identified nodes. We found that the PF group was characterized by lower ICC scores in the right temporo-parietal junction (rTPJ), an area involved in multisensory integration and spatial tasks. The encompassed network revealed PF-related decreases in within- and inter-hemispheric anticorrelations between the rTPJ and the supramarginal gyri, indicating both altered vestibular and self-related functions. Our findings shed light on how the brain copes with gravity transitions, on gravity internalization and are relevant for the understanding of bodily self-consciousness.

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“…Using a custom-made cradle, we were able to record spontaneous BOLD fMRI fluctuations over multiple sessions and create an extensive dataset for fcMRI investigation. Furthermore, we used SE-EPI rather than the more commonly used gradient-echo EPI (GE-EPI) applied in previous rodent fcMRI studies (Liang et al 2012; Lu et al 2012; Grandjean et al 2014; Mechling et al 2014; Nasrallah et al 2014; Sforazzini et al 2014; Stafford et al 2014; Shah et al 2015). While SE-EPI has lower SNR relative to GE-EPI, it is less sensitive to inhomogeneities of the magnetic field, producing less distorted images and enabling better coregistration to a common atlas.…”

Section: Discussionmentioning

confidence: 99%

The Organization of Mouse and Human Cortico-Hippocampal Networks Estimated by Intrinsic Functional Connectivity

et al. 2016

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While the hippocampal memory system has been relatively conserved across mammals, the cerebral cortex has undergone massive expansion. A central question in brain evolution is how cortical development affected the nature of cortical inputs to the hippocampus. To address this question, we compared cortico-hippocampal connectivity using intrinsic functional connectivity MRI (fcMRI) in awake mice and humans. We found that fcMRI recapitulates anatomical connectivity, demonstrating sensory mapping within the mouse parahippocampal region. Moreover, we identified a similar topographical modality-specific organization along the longitudinal axis of the mouse hippocampus, indicating that sensory information arriving at the hippocampus is only partly integrated. Finally, comparing cortico-hippocampal connectivity across species, we discovered preferential hippocampal connectivity of sensory cortical networks in mice compared with preferential connectivity of association cortical networks in humans. Supporting this observation in humans but not in mice, sensory and association cortical networks are connected to spatially distinct subregions within the parahippocampal region. Collectively, these findings indicate that sensory cortical networks are coupled to the mouse but not the human hippocampal memory system, suggesting that the emergence of expanded and new association areas in humans resulted in the rerouting of cortical information flow and dissociation of primary sensory cortices from the hippocampus.

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Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI

Abstract: The results of the current study are important for future studies in mouse models of neurodegenerative disorders, where pharmacological rsfMRI may possibly be used as a non-invasive read-out tool to detect alterations of neurotransmitter systems induced by pathology or treatment.

Cited by 31 publications

References 66 publications

Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain

Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain

Intrinsic functional connectivity reduces after first-time exposure to short-term gravitational alterations induced by parabolic flight

The Organization of Mouse and Human Cortico-Hippocampal Networks Estimated by Intrinsic Functional Connectivity

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