The impact of fasting on resting state brain networks in mice

Abstract Fasting is known to influence learning and memory in mice and alter the neural networks that subserve these cognitive functions. We used high-resolution functional MRI to study the impact of fasting on resting-state functional connectivity in mice following 12 h of fasting. The cortex and subcortex were parcellated into 52 subregions and functional connectivity was measured between each pair of subregions in groups of fasted and non-fasted mice. Functional connectivity was globally increased in the fasted group compared to the non-fasted group, with the most significant increases evident between the hippocampus (bilateral), retrosplenial cortex (left), visual cortex (left) and auditory cortex (left). Functional brain networks in the non-fasted group comprised five segregated modules of strongly interconnected subregions, whereas the fasted group comprised only three modules. The amplitude of low frequency fluctuations (ALFF) was decreased in the ventromedial hypothalamus in the fasted group. Correlation in gamma oscillations derived from local field potentials was increased between the left visual and retrosplenial cortices in the fasted group and the power of gamma oscillations was reduced in the ventromedial hypothalamus. These results indicate that fasting induces profound changes in functional connectivity, most likely resulting from altered coupling of neuronal gamma oscillations

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.

The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its dysfunction might lead to several brain pathologies, including the Alzheimer's disease. A key component of the GS and brain tissue water circulation is the astrocyte which is regulated by acquaporin-4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo and non-invasively

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and diffusion fMRI responses in mouse visual cortex.

The contribution of astrocytes to the BOLD fMRI and DfMRI responses in visual cortex of mice following visual stimulation was investigated using TGN-020, an aquaporin 4 (AQP4) channel blocker, acting as an astrocyte function perturbator. Under TGN-020 injection the amplitude of the BOLD fMRI response became significantly higher. In contrast no significant changes in the DfMRI responses and the electrophysiological responses were observed. Those results further confirm the implications of astrocytes in the neurovascular coupling mechanism underlying BOLD fMRI, but not in the DfMRI responses which remained unsensitive to astrocyte function perturbation

Sedation Agents Differentially Modulate Cortical and Subcortical Blood Oxygenation: Evidence from Ultra-High Field MRI at 17.2 T

<div><p>Background</p><p>Sedation agents affect brain hemodynamic and metabolism leading to specific modifications of the cerebral blood oxygenation level. We previously demonstrated that ultra-high field (UHF) MRI detects changes in cortical blood oxygenation following the administration of sedation drugs commonly used in animal research. Here we applied the UHF-MRI method to study clinically relevant sedation drugs for their effects on cortical and subcortical (thalamus, striatum) oxygenation levels.</p><p>Methods</p><p>We acquired T2*-weighted images of Sprague-Dawley rat brains at 17.2T <i>in vivo</i>. During each MRI session, rats were first anesthetized with isoflurane, then with a second sedative agent (sevoflurane, propofol, midazolam, medetomidine or ketamine-xylazine) after stopping isoflurane. We computed a T2*-oxygenation-ratio that aimed at estimating cerebral blood oxygenation level for each sedative agent in each region of interest: cortex, hippocampus, thalamus and striatum.</p><p>Results</p><p>The T2*-oxygenation-ratio was consistent across scan sessions. This ratio was higher with inhalational agents than with intravenous agents. Under sevoflurane and medetomidine, T2*-oxygenation-ratio was homogenous across the brain regions. Intravenous agents (except medetomidine) induced a T2*-oxygenation-ratio imbalance between cortex and subcortical regions: T2*-oxygenation-ratio was higher in the cortex than the subcortical areas under ketamine-xylazine; T2*-oxygenation-ratio was higher in subcortical regions than in the cortex under propofol or midazolam.</p><p>Conclusion</p><p>Preclinical UHF MRI is a powerful method to monitor the changes in cerebral blood oxygenation level induced by sedative agents across brain structures. This approach also allows for a classification of sedative agents based on their differential effects on cerebral blood oxygenation level.</p></div

Quantitative method for the estimation of regional cerebral blood oxygenation.

<p>T2* magnetic resonance images are acquired at 17.2T in anesthetized rats. Manual segmentation is performed on coronal sections to delineate each region of interest (ROI), here the cortex. For each anesthetic molecule (termed ‘agent’), and for each extracted ROI, the magnetic resonance contrast (C_agent) between the vessels (hypointense) and brain is automatically computed, reflecting the quantity of deoxyHb of the blood <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100323#pone.0100323-Ciobanu1" target="_blank">[6]</a>. The number of voxels of the ROI is also calculated. The index we computed, T2*-oxygenation-ratio, is normalized to the number of voxels of the ROI, and reflects the cerebral blood oxygenation for the ROI and the anesthetic agent <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100323#pone.0100323-Ciobanu1" target="_blank">[6]</a>.</p

Differences of T2*-oxygenation-ratio between anesthetic agents.

<p>A, cortex; B, thalamus; C, hippocampus; D, striatum. Diagrams are box plots made with IBM SPSS software. Each box plot represents median, 25^th and 75^th percentile, minimum and maximum values, outliers (°) and extremes (*). Y-axis: regional T2*-oxygenation-ratio. Compared to isoflurane: # p<0.05, ## p<0.01, ### p<0.001. Compared to sevoflurane: + p<0.05, ++ p<0.01, +++ p<0.001. Compared to midazolam: $p<0.05, ($) p = 0.053. iso, isoflurane; sevo, sevoflurane; prop, propofol; mdz, midazolam; medet, medetomidine; ket-xyl, ketamine-xylazine. The dotted line at 50000 shows a separation between high and low T2*-oxygenation-ratio.</p

Classification of sedative agents based on their effects on the blood oxygenation level assessed by MRI at 17.2 T.

<p>A: The relative oxygenation ratio of isoflurane, sevoflurane, propofol, midazolam, medetomidine and ketamine-xylazine is displayed using a colored disk with variable intensity. Lower color saturation intensity corresponds to lower CBO level, and vice a versa. B: Proposed algorithm to identify anesthetic agents based on relative CBO in the cortex and thalamus as assessed by T2*-oxygenation-ratio. Low signal, T2*-oxygenation-ratio<50000; High signal, T2*-oxygenation-ratio>50000.</p

Magnetic resonance images of the rat brain at 17.2T.

<p>Coronal sections from images that were acquired under different anesthetic agents. T2* magnitude, left panel; T2* phase, middle panel; susceptibility weighted images (SWI), right panel. Red arrowheads refer to hypointense signal corresponding to brain vessels. Images acquired under volatile anesthetic agents (isoflurane A,B,C; sevoflurane D,E,F) display more homogenous MR signal and less contrast between the brain vessels and the brain parenchyma, than intravenous anesthetics (propofol G,H,I; midazolam J,K,L; medetomidine M,N,O; ketamine-xylazine P,Q,R). Green arrowheads refer to hyperintense signal of the sagittal sinus reflecting increased blood oxygenation with isoflurane and sevoflurane as compared to the other anesthetics.</p

fMRI detects bilateral brain network activation following unilateral chemogenetic activation of direct striatal projection neurons

International audienceAbnormal structural and functional connectivity in the striatum during neurological disorders has been reported using functional magnetic resonance imaging (fMRI), although the effects of cell-type specific neuronal stimulation on fMRI and related behavioral alterations are not well understood. In this study, we combined DREADD technology with fMRI ("chemo-fMRI") to investigate alterations of spontaneous neuronal activity. These were induced by the unilateral activation of dopamine D1 receptor-expressing neurons (D1-neurons) in the mouse dorsal striatum (DS). After clozapine (CLZ) stimulation of the excitatory DREADD expressed in D1-neurons, the fractional amplitude of low frequency fluctuations (fALFF) increased bilaterally in the medial thalamus, nucleus accumbens and cortex. In addition, we found that the gamma-band of local field potentials was increased in the stimulated DS and cortex bilaterally. These results provide insights for better interpretation of cell type-specific activity changes in fMRI

Comparison of T2*-oxygenation-ratio of volatile anesthetics among brain regions.

<p>Images are coronal T2* MRI sections acquired <i>in vivo</i> under general anesthesia using isoflurane (A: cortex, B: hippocampus, C: striatum, D: thalamus) or sevoflurane (F: cortex, G: hippocampus, H: striatum, I: thalamus). Box plots represent median, 25^th and 75^th percentile, minimum and maximum values, outliers (°) and extremes (*). Y-axis: regional T2*-oxygenation-ratio. X-axis: Cx, cortex; Hc, hippocampus; Str, stiatum; Th, thalamus. E: T2*-oxygenation-ratio for isoflurane. The thalamus had a lower oxygenation level than the other studied brain regions. J: T2*-oxygenation-ratio for sevoflurane. No significant difference was observed between the studied brain regions. *** p<0.001.</p