NDLI: Functional and Structural Neural Network Characterization of Serotonin Transporter Knockout Rats

Content Provider	PubMed Central
Author	Van, Der Marel Kajo Homberg, Judith R. Otte, Willem M. Dijkhuizen, Rick M.
Editor	Bearer, Elaine L.
Copyright Year	2013
Abstract	Brain serotonin homeostasis is crucially maintained by the serotonin transporter (5-HTT), and its down-regulation has been linked to increased vulnerability for anxiety- and depression-related behavior. Studies in 5-HTT knockout (5-HTT-/-) rodents have associated inherited reduced functional expression of 5-HTT with increased sensitivity to adverse as well as rewarding environmental stimuli, and in particular cocaine hyperresponsivity. 5-HTT down-regulation may affect normal neuronal wiring of implicated corticolimbic cerebral structures. To further our understanding of its contribution to potential alterations in basal functional and structural properties of neural network configurations, we applied resting-state functional MRI (fMRI), pharmacological MRI of cocaine-induced activation, and diffusion tensor imaging (DTI) in 5-HTT-/- rats and wild-type controls (5-HTT+/+). We found that baseline functional connectivity values and cocaine-induced neural activity within the corticolimbic network was not significantly altered in 5-HTT-/- versus 5-HTT+/+ rats. Similarly, DTI revealed mostly intact white matter structural integrity, except for a reduced fractional anisotropy in the genu of the corpus callosum of 5-HTT-/- rats. At the macroscopic level, analyses of complex graphs constructed from either functional connectivity values or structural DTI-based tractography results revealed that key properties of brain network organization were essentially similar between 5-HTT+/+ and 5-HTT-/- rats. The individual tests for differences between 5-HTT+/+ and 5-HTT-/- rats were capable of detecting significant effects ranging from 5.8% (fractional anisotropy) to 26.1% (pharmacological MRI) and 29.3% (functional connectivity). Tentatively, lower fractional anisotropy in the genu of the corpus callosum could indicate a reduced capacity for information integration across hemispheres in 5-HTT-/- rats. Overall, the comparison of 5-HTT-/- and wild-type rats suggests mostly limited effects of 5-HTT genotype on MRI-based measures of brain morphology and function.
Related Links	http://dx.doi.org/10.1371/journal.pone.0057780
Starting Page	57780
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-02-25
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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