Novel method for functional brain imaging in awake minimally restrained rats

Abstract

Functional magnetic resonance imaging (fMRI) in rodents holds great promise for advancing our knowledge about human brain function. However, the use of anesthetics to immobilize rodents during fMRI experiments has restricted the type of questions that can be addressed using this technique. Here we describe an innovative procedure to train rats to be constrained without the need of any anesthesia during the whole procedure. We show that with 8–10 days of acclimation rats can be conscious and remain still during fMRI experiments under minimal stress. In addition, we provide fMRI results of conscious rodents in a variety of commonly used fMRI experimental paradigms, and we demonstrate the improved quality of these scans by comparing results when the same rodents were scanned under anesthesia. We confirm that the awake scanning procedure permits an improved evaluation of brain networks and brain response to external stimuli with minimal movement artifact. The present study further advances the field of fMRI in awake rodents, which provide more direct, forward and reverse, translational opportunities regarding brain functional correspondences between human and rodent research.

An open database of resting-state fMRI in awake rats

“…Neuroscience and psychiatric research have been substantially facilitated by open neuroimaging datasets (Poldrack and Gorgolewski, 2017;Thompson et al, 2014;Van Essen et al, 2013 There has been growing interest in studying brain function and organization in awake rodents using rsfMRI, which avoids interference of anesthesia and permits correlation to behavioral data (Bergmann et al, 2016;Brydges et al, 2013;Chang et al, 2016;Liang et al, 2011;Stenroos et al, 2018;Yoshida et al, 2016). One major challenge of awake rodent fMRI is to control motion and stress during data acquisition.…”

Brain activity for tactile allodynia: a longitudinal awake rat functional magnetic resonance imaging study tracking emergence of neuropathic pain

“…Because pain perception and related behavior require a conscious and aroused state, and because anesthesia dampens BOLD activity, assessment of brain activity in awake animals was deemed critical for accurate identification of tactile allodynia-related brain activity. We therefore used protocols we have recently established for performing fMRI in the awake rat, with proper animal habituation and minimal restraint, permitting brain scans uncontaminated with anesthesia or excessive movement [16]. The main result of this study is that the primary somatosensory cortex likely encodes the intensity of tactile inputs, but does not discriminate nociceptive touch following neuropathic injury.…”

“…There are many challenges in collecting such data, such as excessive movement during scans, and the stress induced during acclimation, which can induce unintended physiological effects [32]. However, we have recently shown that, with proper intstrumental setup and acclimation to the scanning environment [16], animals can remain conscious, still, and feel comfortable during fMRI under minimal stress, entirely without the use of anesthesia. This data is critical to pain research, and we urge others to further improve upon current methods so that the most accurate assessment of conscious pain processing can be captured in the animal brain.…”

“…Rats were habituated to the head-fix system using a short and systematic graded training procedure [16]. The acclimation included 1) body restraint with rats entering a snuggle sack by themselves and assuming a comfortable, natural posture, 2) immobilization of their head with a head-post, 3) air-puff stimulation to their paw, and 4) exposure to loud noise from fMRI scan sequences.…”

Temporal transitions of spontaneous brain activity

“…We used a library of characteristic RSFC patterns as the references Ma Z et al 2016). Each rsfMRI frame was matched to one of 6 (Bergmann E et al 2016;Chang PC et al 2016;Yoshida K et al 2016).…”