Converging structural and functional evidence for a rat salience network

Hot Off the Press – July 17 , 2020.

The human salience network (SN) detects relevant stimuli to guide behavior and is implicated in neuropsychiatric diseases. In this study, we identified a functionally and structurally connected rat SN sharing spatial similarity with humans. We further demonstrated the functional implications of this network with conditioned heroin withdrawal in rats, wherein the rat SN responses to emotionally salient stimuli and reorganizes attention to internal reference. The study provides a translational platform for mechanistic understanding of neuropsychiatric diseases.

Publication Information

Tsai, Pei-Jung; Keeley, Robin J; Carmack, Stephanie A; Vendruscolo, Janaina C M; Lu, Hanbing; Gu, Hong; Vendruscolo, Leandro F; Koob, George F; Lin, Ching-Po; Stein, Elliot A; Yang, Yihong

Converging structural and functional evidence for a rat salience network Journal Article

In: Biological Psychiatry, 2020, ISBN: 0006-3223.

Abstract | Links

@article{Tsai:kq,

title = {Converging structural and functional evidence for a rat salience network},

author = {Pei-Jung Tsai and Robin J Keeley and Stephanie A Carmack and Janaina C M Vendruscolo and Hanbing Lu and Hong Gu and Leandro F Vendruscolo and George F Koob and Ching-Po Lin and Elliot A Stein and Yihong Yang},

url = {https://doi.org/10.1016/j.biopsych.2020.06.023},

isbn = {0006-3223},

year  = {2020},

date = {2020-06-24},

urldate = {2020-06-24},

booktitle = {Biological Psychiatry},

journal = {Biological Psychiatry},

publisher = {Elsevier},

abstract = {Background

The salience network (SN) is dysregulated in many neuropsychiatric disorders, including substance use disorder. Initially described in humans, identification of a rodent SN would provide the ability to mechanistically interrogate this network in preclinical models of neuropsychiatric disorders.



Methods

We used modularity analysis on resting-state functional MRI data of rats (n=32) to parcellate rat insula into functional subdivisions and to identify a potential rat SN based on functional connectivity patterns from the insular subdivisions. We then used mouse tract tracing data from the Allen brain atlas to confirm the network’s underlying structural connectivity. We next compared functional connectivity profiles of the SN across rat, marmoset (n=10) and humans (n=30). Finally, we assessed rat SN’s response to conditioned cues in rats (n=21) with a history of heroin self-administration.



Results

We identified a putative rat SN, which consists of primarily the ventral anterior insula and anterior cingulate cortex, based on functional connectivity patterns from the ventral anterior insular division. Functional connectivity architecture of the rat SN is supported by the mouse neuronal tracer data. Moreover, the anatomical profile of the identified rat SN is similar to that of non-human primates and humans. Finally, we demonstrate that the rat SN responds to conditioned cues and increases functional connectivity to the Default Mode Network during conditioned heroin withdrawal.



Conclusions

The neurobiological identification of a rat SN together with a demonstration of its functional relevance provides a novel platform with which to interrogate its functional significance in normative and neuropsychiatric disease models.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}