Distributed BOLD and CBV-weighted resting-state networks in the mouse brain

Sforazzini, Francesco; Schwarz, Adam J.; Galbusera, Alberto; Bifone, Angelo; Gozzi, Alessandro

doi:10.1016/j.neuroimage.2013.09.050

Cited by 210 publications

(304 citation statements)

References 90 publications

Supporting

Mentioning

270

Contrasting

Order By: Relevance

“…supplementary, barrel field, and visual, and areas proposed to contribute to the "rodent default-mode network" ("DMN"), namely prefrontal and cingulate cortices (Gozzi and Schwarz, 2016;Sforazzini et al, 2014;Stafford et al, 2014). The present findings were robust and reproducible, as evidenced by the similar and significant CPS effects on network strengths obtained in each run, comprising 12-15 mice per CPS and control group per run, and with similar variances observed in the CPS and control data sets.…”

Section: Increases In Within-and Between-network Functional Connectivsupporting

confidence: 78%

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

et al. 2016

View full text Add to dashboard Cite

Human depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward. Using multimodal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we investigated CPS effects on function and structure in the mouse brain under light anesthesia. Mice underwent a baseline MRI/MRS session, followed by 15-day CPS (n=26) or control handling (n=27), and a post-treatment MRI/MRS session. In BOLD fMRI, relative to controls, CPS mice exhibited robust, reproducible increases in FC within 8 of 9 identified cortical networks, including the prefrontal and cingulate cortices that contribute to the "mouse DMN". CPS mice exhibited increases in between-network FC, including amygdala -prefrontal cortex and amygdala -cingulate cortex. MRS identified metabolic alterations in CPS mice as increased inositol levels in amygdala and increased glycerophosphorylcholine levels in prefrontal cortex. Diffusion-weighted MRI detected increased fractional anisotropic values in the cingulum. This study demonstrates that chronic psychosocial stress induces FC states in the mouse brain analogous to those observed in depression, as well as cerebral metabolism and white matter pathway alterations that contribute to understanding of pathological processes. It also demonstrates the importance of brain imaging to the establishment of valid animal models in translational psychiatry. AbstractHuman depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward.Using multimodal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we investigated CPS effects on function and structure in the mouse brain under light anesthesia. Mice underwent a baseline MRI/MRS session, followed by 15-day CPS (n=26) or control handling (n=27), and a posttreatment MRI/MRS session. In BOLD fMRI, relative to controls, CPS mice exhibited robust, reproducible increases in FC within 8 of 9 identified cortical networks, including the prefrontal and cingulate cortices that contribute to the "mouse DMN". CPS mice exhibited increases in b...

show abstract

Section: Increases In Within-and Between-network Functional Connectivsupporting

confidence: 78%

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

et al. 2016

View full text Add to dashboard Cite

show abstract

“…24,25 Cortico-hippocampal connectivity was mapped with respect to a bilateral seed region placed in ventral hippocampus (subiculum), a key component of a distributed fronto-hippocampal network that appears to be conserved in rodents and humans. 30,51 The connectivity profile of the hippocampus in control mice highlighted the involvement of frontal and cingulate cortices (Figure 4a), in agreement with previous reports. 30,33,51 Interestingly, although the strength of hippocampal-frontal connectivity was similar in the two genotypes, the connectional profile of this region in Ddo − / − mice appeared to exhibit a wider and stronger involvement of peri-hippocampal and parietal somatosensory areas (P o 0.01, Student's t-test; Figures 4b and c).…”

Section: Resultssupporting

confidence: 91%

“…30,51 The connectivity profile of the hippocampus in control mice highlighted the involvement of frontal and cingulate cortices (Figure 4a), in agreement with previous reports. 30,33,51 Interestingly, although the strength of hippocampal-frontal connectivity was similar in the two genotypes, the connectional profile of this region in Ddo − / − mice appeared to exhibit a wider and stronger involvement of peri-hippocampal and parietal somatosensory areas (P o 0.01, Student's t-test; Figures 4b and c). We detected no significant confounding effect of genotype on depth of anesthesia during fMRI as assessed by the amplitude of cortical BOLD signal fluctuation, 33,52 which was comparable in the two genotypes (62.9 ± 2.9 and 65.4 ± 2.9, respectively, P = 0.49, Student's t-test).…”

Section: Resultssupporting

confidence: 91%

“…30,33 Clinical and preclinical evidence supports the presence of cortico-hippocampal dysconnectivity in SCZ, a feature that seems to predominantly affect fronto-cortical areas, 24 with the additional involvement of large parietal and perihippocampal cortical regions. 25 Interestingly, although the strength of hippocampal-frontal connectivity was similar in the two genotypes, our rsfMRI measurements suggest that elevated DAsp levels can reshape the connectional profile of the hippocampus, resulting in stronger and more widespread peri-hippocampal and parietal-hippocampal connectivity in knockout brains.…”

Section: Discussionmentioning

confidence: 95%

“…30,33 Small a priori seed regions were chosen to cover anteroposterior cortical and hippocampal networks. The fMRI response to PCP was mapped and quantified as previously described.…”

Section: Functional and Pharmacological Magnetic Resonance Imagingmentioning

confidence: 99%

See 2 more Smart Citations

A Role for D-aspartate Oxidase in Schizophrenia and in Schizophrenia-related Symptoms Induced by Phencyclidine in Mice.

Squillace

Errico

D’Argenio

et al. 2015

European Psychiatry

View full text Add to dashboard Cite

Increasing evidence points to a role for dysfunctional glutamate N-methyl-D-aspartate receptor (NMDAR) neurotransmission in schizophrenia. D-aspartate is an atypical amino acid that activates NMDARs through binding to the glutamate site on GluN2 subunits. D-aspartate is present in high amounts in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-aspartate oxidase (DDO). The agonistic activity exerted by D-aspartate on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for some of the NMDAR-related alterations observed in schizophrenia. Consistently, substantial reductions of D-aspartate and NMDA were recently observed in the postmortem prefrontal cortex of schizophrenic patients. Here we show that DDO mRNA expression is increased in prefrontal samples of schizophrenic patients, thus suggesting a plausible molecular event responsible for the D-aspartate imbalance previously described. To investigate whether altered D-aspartate levels can modulate schizophrenia-relevant circuits and behaviors, we also measured the psychotomimetic effects produced by the NMDAR antagonist, phencyclidine, in Ddo knockout mice (Ddo −/ − ), an animal model characterized by tonically increased D-aspartate levels since perinatal life. We show that Ddo − / − mice display a significant reduction in motor hyperactivity and prepulse inhibition deficit induced by phencyclidine, compared with controls. Furthermore, we reveal that increased levels of D-aspartate in Ddo − / − animals can significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico-hippocampal connectivity networks potentially involved in schizophrenia. Collectively, the present results suggest that altered D-aspartate levels can influence neurodevelopmental brain processes relevant to schizophrenia.

show abstract

Mapping the Connectional Architecture of the Rodent Brain with fMRI

Schwarz

Gozzi

2017

Handbook of Neurobehavioral Genetics and Phenotyping

View full text Add to dashboard Cite

Distributed BOLD and CBV-weighted resting-state networks in the mouse brain

Cited by 210 publications

References 90 publications

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

A Role for D-aspartate Oxidase in Schizophrenia and in Schizophrenia-related Symptoms Induced by Phencyclidine in Mice.

Mapping the Connectional Architecture of the Rodent Brain with fMRI

Contact Info

Product

Resources

About