Stress-induced alterations in large-scale functional networks of the rodent brain

Henckens, Marloes J. A. G.; Marel, Kajo van der; Toorn, Annette van der; Pillai, Anup G.; Fernández, Guillén; Dijkhuizen, Rick M.; Joëls, Marian

doi:10.1016/j.neuroimage.2014.10.037

Cited by 99 publications

(109 citation statements)

References 93 publications

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“…A recent MRI study of chronic immobilization stress in rat, also using group ICA, identified similar networks and, in agreement with the present study, stressed rats exhibited cortical network-specific increases in FC in visual and somatosensory cortices as well as in "DMN" (defined as orbitofrontal, medial prefrontal, cingulate, retrosplenial parietal and medial visual cortices and hippocampus); motor, PFC and ACC, and four subcortical networks, were unaffected (Henckens et al, 2015). Therefore, both chronic physical stress in rat and CPS in mouse increased FC within cortical networks in lightly anesthetized subjects.…”

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

confidence: 92%

“…Decreased hippocampal volume was reported in rat following chronic unpredictable mild stress for 8 but not 2 weeks (Luo et al, 2014), suggesting that a certain chronicity of stress might need to elapse to induce volume reduction. Chronic immobilization stress in rat was without effect on hippocampal volume (Henckens et al, 2015). In mice that were susceptible to CSD in terms of decreased social avoidance, there was no increase in hippocampal volume post-versus pre-CSD, whereas there was an increase in hippocampal volume in control and resilient CSD mice (Tse et al, 2014).…”

Section: Metabolic and Structural Changes In Cps Micementioning

confidence: 85%

“…If analogous brain changes can be identified, the animal models provide a unique opportunity to study the underlying cellular and molecular processes. In rats, a recent rs-fMRI study demonstrated that the physical stressor of repeated immobilisation results in increased FC within the "DMN" as well as somatosensory-cortex and visual-cortex networks (Henckens et al, 2015). In mice, rs-fMRI has been applied to demonstrate that structurally connected brain areas also exhibit FC, that brain topology and networks exhibit homology with primate species (Stafford et al, 2014), and that network alterations are sensitive indicators of pathology (Grandjean et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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...

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

confidence: 92%

Section: Metabolic and Structural Changes In Cps Micementioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…49 The changed activity within the DMN in response to chronic stress exposure has been found in humans 50 and animals. 51 The impairment of cortical structures in HA Tibetans is likely to reflect the stress-induced atrophic effects in cortical regions. Cortical atrophy within the DMN may reduce the brain response to HA environmental stress.…”

Section: Implications For the Changes In Cortical Structural Measuremmentioning

confidence: 99%

Cortical Thickness of Native Tibetans in the Qinghai-Tibetan Plateau

Wang

Gong

et al. 2017

AJNR Am J Neuroradiol

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“…Imaging studies have demonstrated that traumatic events alter functional connectivity of the prefrontal cortex in humans (Krause-Utz et al, 2014; Lanius et al, 2010;Long et al, 2014;van Wingen et al, 2012) and rodents (Henckens et al, 2015;Liang et al, 2014), but synaptic process underlying such changes remains largely unexplored. To that end, we examined OF-induced synaptic adaptations in PCs in dmPFC layer V, which are one of the major outputs of dmPFC.…”

Section: Discussionmentioning

confidence: 99%

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

Liu

Ito

Morozov

2016

Neuropsychopharmacol

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The observational fear (OF) paradigm in rodents, in which the subject is exposed to a distressed conspecific, elicits contextual fear learning and enhances future passive avoidance learning, which may model certain behavioral traits resulting from traumatic experiences in humans. As these behaviors affected by the OF require dorso-medial prefrontal cortex (dmPFC), we searched for synaptic adaptations in dmPFC resulting from OF in mice by recording synaptic responses in dmPFC layer V pyramidal neurons elicited by repeated 5 Hz electrical stimulation of dmPFC layer I or by optogenetic stimulation of specific interneurons ex vivo 1 day after OF. OF increased depression of inhibitory postsynaptic currents (IPSCs) along IPSC trains evoked by the 5 Hz electrical stimulation, but, surprisingly, decreased depression of dendritic IPSCs isolated after blocking GABAa receptor on the soma. Subsequent optogenetic analyses revealed increased depression of IPSCs originating from perisomatically projecting parvalbumin interneurons (PV-IPSCs), but decreased depression of IPSCs from dendritically projecting somatostatin cells (SOM-IPSCs). These changes were no longer detectable in the presence of a GABAb receptor antagonist CGP52432. Meanwhile, OF decreased the sensitivity of SOM-IPSCs, but not PV-IPSCs to a GABAb receptor agonist baclofen. Thus, OF causes opposing changes in GABAb receptor mediated suppression of GABA release from PV-positive and SOM-positive interneurons. Such adaptations may alter dmPFC connectivity with brain areas that target its deep vs superficial layers and thereby contribute to the behavioral consequences of the aversive experiences.

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Stress-induced alterations in large-scale functional networks of the rodent brain

Cited by 99 publications

References 93 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

Cortical Thickness of Native Tibetans in the Qinghai-Tibetan Plateau

GABAb Receptor Mediates Opposing Adaptations of GABA Release From Two Types of Prefrontal Interneurons After Observational Fear

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