Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation fMRI

Abstract

Since its discovery in the early 90s, BOLD signal-based functional Magnetic Resonance Imaging (fMRI) has become a fundamental technique for the study of brain activity in basic and clinical research. Functional MRI signals provide an indirect but robust and quantitative readout of brain activity through the tight coupling between cerebral blood flow and neuronal activation, the so-called neurovascular coupling. Combined with experimental techniques only available in animal models, such as intracerebral micro-stimulation, optogenetics or pharmacogenetics, provides a powerful framework to investigate the impact of specific circuit manipulations on overall brain dynamics. The purpose of this chapter is to provide a comprehensive protocol to measure brain activity using fMRI with intracerebral electric micro-stimulation in murine models. Preclinical research (especially in rodents) opens the door to very sophisticated and informative experiments, but at the same time imposes important constrains (i.e., anesthetics, translatability), some of which will be addressed here.

Transient Hypothyroidism During Lactation Alters the Development of the Corpus Callosum in Rats. An in vivo Magnetic Resonance Image and Electron Microscopy Study

“…The coronal and sagittal planes of study were determined from preliminary T2-weighted (T2w) images acquired in the three orthogonal planes using rapid acquisition relaxation enhanced sequence (RARE) with the following parameters: RARE factor 8, 15 slices, slice thickness 1 mm, field of view (FOV) 40 mm × 40 mm, matrix 256 × 256, effective echo time (TE eff ) 56 ms, repetition time (TR) 2,000 ms, 1 average for 1 min 4 s total acquisition time ( Hennig and Friedburg, 1988 ; Perez-Cervera et al, 2018 ). Using these anatomical images, final coronal MRI images were acquired using RARE sequence with the following parameters: RARE factor 8, 25 slices, slice thickness 0.5 mm, FOV 20 mm × 20 mm, matrix 200 × 200 (voxel size 100 μm × 100 μm × 500 μm), TE eff 56 ms, TR 3,728 ms, 4 averages for 12 min 26 s total acquisition time ( Lucia et al, 2018 ).…”

Transient Hypothyroidism During Lactation Arrests Myelination in the Anterior Commissure of Rats. A Magnetic Resonance Image and Electron Microscope Study

“…Due to the AC antero-posterior diameter (ranging from 505 μm in P8 MMI E10 to 850 μm in P365 C rats) and MRI section thickness (500 μm), selection of the optimal coronal plane of study was crucial in order to avoid partial volume effects (i.e., gray matter overlap in AC). The final plane of study was determined from preliminary T2-weighted (T2w) images acquired in the three orthogonal planes using rapid acquisition relaxation enhanced sequence (RARE) with the following parameters: RARE factor 8, 15 slices, slice thickness 1 mm, field of view (FOV) 40 mm × 40 mm, matrix 256 × 256, effective echo time (TE eff ) 56 ms, repetition time (TR) 2000 ms, 1 average for 1 min 4 s total acquisition time ( Hennig and Friedburg, 1988 ; Perez-Cervera et al, 2018 ). Using these anatomical images, final coronal MRI images were acquired using RARE sequence with the following parameters: RARE factor 8, 25 slices, slice thickness 0.5 mm, FOV 20 mm × 20 mm, matrix 200×200 (voxel size 100 μm × 100 μm × 500 μm), TE eff 56 ms, TR 3,728 ms, four averages for 12 min 26 s total acquisition time.…”

TherMouseDuino: An affordable Open-Source temperature control system for functional magnetic resonance imaging experimentation with mice

“…These experiments require long periods of brain imaging to monitor longitudinally the consequences of short-and long-term plasticity. During the complete recording time, the physiology of the animal needs to be exquisitely constant, in order to preserve the quantitative value of the BOLD signals [11,16,35]. Only a control experiment without induction of synaptic plasticity is shown in Figure 7C, to illustrate the high stability of the signal in time.…”

“…Mice were anaesthetized with urethane (1.4 g/kg) and fixed in a stereotaxic frame (Narishigue, Tokyo, Japan). We placed a custom made carbon fibre MRI-compatible electrode [16,51] of voxel time series, a general linear model (GLM) was applied. Functional maps were generated from voxels that had a higher significance than p < 0.01.…”

“…Currently, preclinical research is a fundamental step preceding the translation of scientific findings to clinical application in humans. In most of these investigations, anesthetized animals are used to study cerebral function [14,15,16] The main reason for the use of anesthetics is that brain imaging requires immobilization of the subject inside the magnet, to generate meaningful and high signal-to-noise datasets. Immobilization, however, is a well-known stressor that induces important physiological changes that can severely influence the experimental results [17].…”