Abstract
Reciprocal neuronal connections exist between the internal organs of the body and the nervous system. These projections to and from the viscera play an essential role in maintaining and finetuning organ responses in order to sustain homeostasis and allostasis. Functional maps of brain regions participating in this bidirectional communication have been previously studied in awake humans and anesthetized rodents. To further refine the mechanistic understanding of visceral influence on brain states, however, new paradigms that allow for more invasive, and ultimately more informative, measurements and perturbations must be explored. Further, such paradigms should prioritize human translatability. In the current paper, we address these issues by demonstrating the feasibility of non-anesthetized animal imaging during visceral manipulation. More specifically, we used a barostat interfaced with an implanted gastric balloon to cyclically induce distension of a non-anesthetized male rat’s stomach during simultaneous BOLD fMRI. General linear modeling and spatial independent component analysis revealed several regions with BOLD activation temporally coincident with the gastric distension stimulus. The ON-OFF (20 mmHg - 0 mmHg) barostat-balloon pressure cycle resulted in widespread BOLD activation of the inferior colliculus, cerebellum, ventral midbrain, and a variety of hippocampal structures. These results suggest that neuroimaging models of gastric manipulation in the non-anesthetized rat are achievable and provide an avenue for more comprehensive studies involving the integration of other neuroscience techniques like electrophysiology.
Significance Statement It is unclear to what extent measurements of brain activity are affected by interoceptive processes. To advance our understanding of ongoing visceral activity’s influence on brain states, here we provide a proof of concept, anesthesia-free animal model of visceral manipulation during simultaneous BOLD fMRI. We successfully demonstrated BOLD activation during gastric distension of the unanesthetized rat in both classically reported (cerebellum, hippocampus) and novel (inferior colliculus) regions. This paradigm establishes an important foundation for further interrogation of viscera-brain interactions.
Footnotes
We thank Drs. Shiying Li, Jiande Chen and Zhongming Liu for their technical support. The present study was partially supported by National Center for Complementary and Integrative Health (R01AT011665) and National Institute of Neurological Disorders and Stroke (R01NS085200). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The authors declare no competing financial interests.
↵#These authors contributed equally to this work.
