DOI: 10.5061/dryad.1rn8pk0q9
title: Data from: Brain functional networks associated with social bonding in monogamous voles

description: Previous studies have related pair bonding in Microtus ochrogaster, the
 prairie vole, with plastic changes in several brain regions. However, the
 interactions between these socially-relevant regions have yet to be
 described. In this study, we used resting state magnetic resonance imaging
 to explore bonding behaviors and functional connectivity of brain regions
 previously associated with pair bonding. Thirty-two male and female
 prairie voles were scanned at baseline, 24h and 2 weeks after the onset of
 cohabitation. By using network based statistics, we identified that the
 functional connectivity of a cortico-striatal network predicted the onset
 of affiliative behavior, while another predicted the amount of social
 interaction during a partner preference test. Furthermore, a network with
 significant changes in time was revealed, also showing associations with
 the level of partner preference. Overall, our findings revealed the
 association between network-level functional connectivity changes and
 social bonding.
description: Thirty-two three-month-old sexually
 naïve female (<i>N</i>=16) and male (<i>N</i>=16)
 prairie voles (<i>Microtus ochrogaster</i>) were used in the
 study. The animals were housed in a temperature (23°C) and light (14:10
 light-dark cycle) controlled room and provided with rabbit diet HF-5326
 (LabDiet, St. Louis, MO, USA) oat, sunflower seeds, and water <i>ad
 libitum</i>. These voles were previously weaned at 21 days, housed
 in same-sex cages, and were descendants of voles generously donated by Dr.
 Larry J. Young from his colony at Emory University. The animal research
 protocols were approved by the bioethics committee of the Instituto de
 Neurobiología, UNAM. Fourteen
 days before the experimental protocol, female voles were bilaterally
 ovariectomized. After recovery, silastic capsules (Dow Corning™ Silastic™
 Laboratory Tubing; Thermo Fisher Scientific, Pittsburg, USA) containing
 estradiol benzoate (E2B; Sigma Aldrich, Missouri, USA) dissolved in corn
 oil (0.5 mg/mL of E2B) were implanted via s.c. to induce sexual
 receptivity four days before cohabitation protocol and remained implanted
 during the entire experimental protocol. Prairie
 voles underwent three MRI acquisition sessions: a baseline scan before
 cohabitation, a second scan after 24 hours of cohabitation, and a third
 scan after two weeks of cohabitation. The day after the baseline scanning
 session, female and male voles unrelated to each other were randomly
 assigned as couples and placed for cohabitation in a new home cage with
 fresh bedding to promote <i>ad libitum </i>mating and social
 interaction. Voles were housed in couples for the remainder of the
 experiment and were only separated for MRI scanning sessions and
 behavioral tests. Animals were
 anesthetized to avoid stress and excessive movement during scanning
 sessions. Isoflurane at 3% concentration in an oxygen mixture was used for
 induction and positioning in the scanner bed, in which the head was
 immobilized with a bite bar and the coil head holder. Once voles were
 securely placed in the scanner bed, isoflurane anesthesia was adjusted at
 a 2% concentration and a single bolus of 0.05 mg/kg of dexmedetomidine
 (Dexdomitor; Zoetis, Mexico) was administered subcutaneously. Five minutes
 after the bolus injection, isoflurane anesthesia was lowered and
 maintained at 0.5%. MRI acquisition started when physiological readings
 were stabilized (~15 minutes after bolus injection). Body temperature was
 maintained with a circulating water heating pad within the scanner bed
 (Supplementary Figure 1), respiration rate was monitored with an
 MR-compatible pneumatic pillow sensor, and blood oxygen saturation was
 measured with an MR-compatible infrared pulse-oximeter (SA instruments
 Inc, Stony Brook NY). After the scanning sessions, animals were monitored
 until fully recovered and transferred back to their housing.
 Prairie voles underwent three MRI
 acquisition sessions: a baseline scan before cohabitation, a second scan
 24h after the onset of cohabitation, and a third scan 2 weeks after the
 onset of cohabitation. MRI acquisition was conducted with a Bruker
 Pharmascan 70/16US, 7 Tesla magnetic resonance scanner (Bruker, Ettlingen,
 Germany), using an MRI CryoProbe transmit/receive surface coil (Bruker,
 Ettlingen, Germany). Paravision-6 (Bruker, Ettlingen, Germany) was used to
 perform all imaging protocols. Before running the fMRI sequence, local
 field homogeneity was optimized within an ellipsoid covering the whole
 brain and skull using previously acquired field maps. rsfMRI was acquired
 using a spin-echo echo planar imaging (SE-EPI) sequence: repetition time
 (TR) = 2000 ms, echo time (TE) = 19 ms, flip angle (FA) = 90°, field of
 view (FOV) = 18 × 16 mm<sup>2</sup>, matrix dimensions = 108 ×
 96, yielding an in-plane voxel dimensions of 0.167 × 0.167
 mm<sup>2</sup>, and slice thickness of 0.7 mm, total volumes
 acquired = 305 (10 minutes and 10 seconds). EPI bandwidth was
 288461.5 Hz, the number of slices was 25, pi pulse (refocusing pulse)
 duration was 1.5455 ms with 2200.0 Hz bandwidth, and pi/2 (excitation
 pulse) was 1.9091 ms and 2200.0 Hz, respectively. After the rsfMRI sequence, an
 anatomical scan was obtained using a spin-echo rapid acquisition with
 refocused echoes (Turbo-RARE) sequence with the following parameters: TR =
 1800 ms, TE = 38 ms, RARE factor = 16, number of averages (NA) = 2, FOV =
 18 × 20 mm<sup>2</sup>, matrix dimensions = 144 × 160, slice
 thickness = 0.125 mm, resulting in isometric voxels of size 0.125 × 0.125
 × 0.125 mm<sup>3</sup>.
 Imaging data preprocessing was
 performed with FMRIB’s Software Libraries (FSL, RRID:SCR_002823; Jenkinson
 et al., 2012) and Advanced Normalization Tools (ANTs; RRID:SCR_004757;
 Avants et al., 2011) for spatial registration. To avoid initial signal
 instability, the first 5 volumes of each functional series were discarded.
 Slice-timing correction and motion correction were applied using the first
 non-discarded volume as reference. The reference volume was also taken to
 determine the deformable transformation to the corresponding anatomical
 image. The resulting transformation was combined with a non-linear
 transformation to a prairie vole brain template obtained from previously
 published work (Ortiz et al., 2018). Functional images were later warped
 to the brain template and resampled to resolution of 0.16 × 0.16 × 0.7
 mm3. To minimize physiological
 confounds, the first 5 eigenvectors (time-series) within the combined
 non-grey matter mask were obtained (Behzadi et al., 2007), since
 recent findings have shown that vascular, ventricle, and
 white matter signal regression enhances functional connectivity
 specificity from rsfMRI data (Grandjean et al., 2020). These eigenvectors and the 6
 motion parameters (3 rotations, 3 displacements) were regressed out from
 each subject’s functional series. Datasets were band-pass filtered to
 retain frequencies between 0.01 and 0.1 Hz (Gorges et al., 2017). Finally,
 smoothing was applied with a box kernel with size of three voxels, using
 FSL (RRID:SCR_002823).
description: Due to technical problems, two subjects missed the baseline MRI
 acquisition (session 1), and two subjects missed the 2 week-cohabitation
 MRI acquisition (session 3). Additionally, two datasets of session 1
 showed signal loss in the posterior cortex. The final sampling consisted
 of 90 datasets, with only 6 subjects missing one session.
 README file for recommendations in data usage is also
 included.