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

被引:0
作者
Disha Shah
Ines Blockx
Georgios A. Keliris
Firat Kara
Elisabeth Jonckers
Marleen Verhoye
Annemie Van der Linden
机构
[1] University of Antwerp,Bio
[2] Max Planck Institute for Biological Cybernetics,Imaging Lab
来源
Brain Structure and Function | 2016年 / 221卷
关键词
Cholinergic; Serotonergic; Functional connectivity; Default-mode network; Functional networks; Mouse brain;
D O I
暂无
中图分类号
学科分类号
摘要
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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页码:3067 / 3079
页数:12
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共 316 条
[1]  
Albert PR(2014)Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: pivotal role of pre- and post-synaptic 5-HT1A receptor expression Front Behav Neurosci 8 199-1265
[2]  
Vahid-Ansari F(2011)Scopolamine disrupts hippocampal activity during allocentric spatial memory in humans: an fMRI study using a virtual reality analogue of the Morris Water Maze J Psychopharmacol 25 1256-4340
[3]  
Luckhart C(2012)Bidirectional relationship between functional connectivity and amyloid-beta deposition in mouse brain J Neurosci 32 4334-1658
[4]  
Antonova E(2009)Contribution of the striatum to the effects of 5-HT1A receptor stimulation in L-DOPA-treated hemiparkinsonian rats J Neurosci Res 87 1645-541
[5]  
Parslow D(1995)Functional connectivity in the motor cortex of resting human brain using echo-planar MRI Magn Reson Med 34 537-311
[6]  
Brammer M(2014)Network dysfunction in Alzheimer’s disease: refining the disconnection hypothesis Brain Connect 4 299-296
[7]  
Simmons A(2009)Default-mode brain dysfunction in mental disorders: a systematic review Neurosci Biobehav Rev 33 279-38
[8]  
Williams S(2008)The brain’s default network: anatomy, function, and relevance to disease Ann N Y Acad Sci 1124 1-1873
[9]  
Dawson GR(2009)Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer’s disease J Neurosci 29 1860-198
[10]  
Morris R(2009)Complex brain networks: graph theoretical analysis of structural and functional systems Nat Rev Neurosci 10 186-74