Biology subjects

Neuberger, T.

Publications and source records attributed to Neuberger, T..

3 recordsLinked to original sources

bioRxiv2024

Neuroimaging model of visceral manipulation in awake rat

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 rats 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 StatementIt is unclear to what extent measurements of brain activity are affected by background, and experimentally unrelated, interoceptive processes. To advance our understanding of ongoing visceral activitys 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.

neuroscience↗

bioRxiv2023

A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and alleviates experimental atherosclerosis

Ketogenic diets (KD) are very low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. In this study, we used apolipoprotein E deficient (ApoE -/-) mice to investigate the vascular impact and plasma metabolic signature of a very high-fat KD compared to a non-ketogenic high-fat diet (HFD). Plasma samples were collected after 4, 8, and 12 weeks on the experimental diets and used to quantify the major ketone body {beta}-hydroxybutyrate (BHB), inflammatory cytokines (interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1; and tumor necrosis factor , TNF-), and targeted metabolomic profiling by mass spectrometry. Moreover, aortic atherosclerotic lesions were quantified ex vivo by magnetic resonance imaging (MRI) on a 14-tesla system. The results showed that, relative to HFD mice, the KD mice had markedly higher levels of BHB and lower levels of cytokines, confirming the presence of ketosis that alleviated the well-established fat-induced systemic inflammation. Moreover, mice under nutritional ketosis displayed a distinct plasma amino acid profile evidencing a KD-induced alteration in protein metabolism. Significant changes in the plasma metabolome in KD mice included a decrease in lipophilic and increase in hydrophilic metabolites. Despite the higher fat content of the KD versus the HFD, KD mice presented significantly lower levels of several lipid metabolites, including phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides. Consistent with the shift in energy metabolism toward fatty acid oxidation caused by the KD, the ratio of acylcarnitines to free carnitine was significantly higher in KD than in HFD mice., the aortic plaque burden was significantly lower in the KD versus the HFD group. In conclusion, nutritional ketosis induced by the KD was associated with specific metabolic changes and an atheroprotective phenotype versus the HFD.

biochemistry↗

bioRxiv2019

Global brain signal in awake rats

Although often used as a nuisance in resting-state functional magnetic resonance imaging (rsfMRI), the global brain signal in humans and anesthetized animals has important neural basis. However, our knowledge of the global signal in awake rodents is sparse. To bridge this gap, we systematically analyzed rsfMRI data acquired with a conventional single-echo (SE) echo planar imaging (EPI) sequence in awake rats. The spatial pattern of rsfMRI frames during peaks of the global signal exhibited prominent co-activations in the thalamo-cortical and hippocampo-cortical networks, as well as in the basal forebrain, hinting that these neural networks might contribute to the global brain signal in awake rodents. To validate this concept, we acquired rsfMRI data using a multi-echo (ME) EPI sequence and removed non-neural components in the rsfMRI signal. Consistent co-activation patterns were obtained in extensively de-noised ME-rsfMRI data, corroborating the finding from SE-rsfMRI data. Furthermore, during rsfMRI experiments we simultaneously recorded neural spiking activities in the hippocampus using GCaMP-based fiber photometry. The hippocampal calcium activity exhibited significant correspondence with the global rsfMRI signal. These data collectively suggest that the global rsfMRI signal contains significant neural components that involve coordinated activities in the thalamo-cortical and hippocampo-cortical networks. These results provide important insight into the neural substrate of the global brain signal in awake rodents.

neuroscience↗