Chemogenetic activation of mammalian brain neurons expressing insect Ionotropic Receptors by systemic ligand precursor administration.

Chemogenetic approaches employing ligand-gated ion channels are advantageous regarding manipulation of target neuronal population functions independently of endogenous second messenger pathways. Among them, Ionotropic Receptor (IR)-mediated neuronal activation (IRNA) allows stimulation of mammalian neurons that heterologously express members of the insect chemosensory IR repertoire in response to their cognate ligands. In the original protocol, phenylacetic acid, a ligand of the IR84a/IR8a complex, was locally injected into a brain region due to its low permeability of the blood-brain barrier. To circumvent this invasive injection, we sought to develop a strategy of peripheral administration with a precursor of phenylacetic acid, phenylacetic acid methyl ester, which is efficiently transferred into the brain and converted to the mature ligand by endogenous esterase activities. This strategy was validated by electrophysiological, biochemical, brain-imaging, and behavioral analyses, demonstrating high utility of systemic IRNA technology in the remote activation of target neurons in the brain.

Silencing dentate newborn neurons alters excitatory/inhibitory balance and impairs behavioral inhibition and flexibility.

Adult neurogenesis confers the hippocampus with unparalleled neural plasticity, essential for intricate cognitive functions. The specific influence of sparse newborn neurons (NBNs) in modulating neural activities and subsequently steering behavior, however, remains obscure. Using an engineered NBN-tetanus toxin mouse model (NBN-TeTX), we noninvasively silenced NBNs, elucidating their crucial role in impulse inhibition and cognitive flexibility as evidenced through Morris water maze reversal learning and Go/Nogo task in operant learning. Task-based functional MRI (tb-fMRI) paired with operant learning revealed dorsal hippocampal hyperactivation during the Nogo task in male NBN-TeTX mice, suggesting that hippocampal hyperexcitability might underlie the observed behavioral deficits. Additionally, resting-state fMRI (rs-fMRI) exhibited enhanced functional connectivity between the dorsal and ventral dentate gyrus following NBN silencing. Further investigations into the activities of PV+ interneurons and mossy cells highlighted the indispensability of NBNs in maintaining the hippocampal excitation/inhibition balance. Our findings emphasize that the neural plasticity driven by NBNs extensively modulates the hippocampus, sculpting inhibitory control and cognitive flexibility.

Functional ultrasound reveals effects of MRI acoustic noise on brain function.

Loud acoustic noise from the scanner during functional magnetic resonance imaging (fMRI) can affect functional connectivity (FC) observed in the resting state, but the exact effect of the MRI acoustic noise on resting state FC is not well understood. Functional ultrasound (fUS) is a neuroimaging method that visualizes brain activity based on relative cerebral blood volume (rCBV), a similar neurovascular coupling response to that measured by fMRI, but without the audible acoustic noise. In this study, we investigated the effects of different acoustic noise levels (silent, 80 dB, and 110 dB) on FC by measuring resting state fUS (rsfUS) in awake mice in an environment similar to fMRI measurement. Then, we compared the results to those of resting state fMRI (rsfMRI) conducted using an 11.7 Tesla scanner. RsfUS experiments revealed a significant reduction in FC between the retrosplenial dysgranular and auditory cortexes (0.56 ± 0.07 at silence vs 0.05 ± 0.05 at 110 dB, p=.01) and a significant increase in FC anticorrelation between the infralimbic and motor cortexes (-0.21 ± 0.08 at silence vs -0.47 ± 0.04 at 110 dB, p=.017) as acoustic noise increased from silence to 80 dB and 110 dB, with increased consistency of FC patterns between rsfUS and rsfMRI being found with the louder noise conditions. Event-related auditory stimulation experiments using fUS showed strong positive rCBV changes (16.5% ± 2.9% at 110 dB) in the auditory cortex, and negative rCBV changes (-6.7% ± 0.8% at 110 dB) in the motor cortex, both being constituents of the brain network that was altered by the presence of acoustic noise in the resting state experiments. Anticorrelation between constituent brain regions of the default mode network (such as the infralimbic cortex) and those of task-positive sensorimotor networks (such as the motor cortex) is known to be an important feature of brain network antagonism, and has been studied as a biological marker of brain disfunction and disease. This study suggests that attention should be paid to the acoustic noise level when using rsfMRI to evaluate the anticorrelation between the default mode network and task-positive sensorimotor network.

Brain-wide mapping of resting-state networks in mice using high-frame rate functional ultrasound.

Functional ultrasound (fUS) imaging is a method for visualizing deep brain activity based on cerebral blood volume changes coupled with neural activity, while functional MRI (fMRI) relies on the blood-oxygenation-level-dependent signal coupled with neural activity. Low-frequency fluctuations (LFF) of fMRI signals during resting-state can be measured by resting-state fMRI (rsfMRI), which allows functional imaging of the whole brain, and the distributions of resting-state network (RSN) can then be estimated from these fluctuations using independent component analysis (ICA). This procedure provides an important method for studying cognitive and psychophysiological diseases affecting specific brain networks. The distributions of RSNs in the brain-wide area has been reported primarily by rsfMRI. RSNs using rsfMRI are generally computed from the time-course of fMRI signals for more than 5 min. However, a recent dynamic functional connectivity study revealed that RSNs are still not perfectly stable even after 10 min. Importantly, fUS has a higher temporal resolution and stronger correlation with neural activity compared with fMRI. Therefore, we hypothesized that fUS applied during the resting-state for a shorter than 5 min would provide similar RSNs compared to fMRI. High temporal resolution rsfUS data were acquired at 10 Hz in awake mice. The quality of the default mode network (DMN), a well-known RSN, was evaluated using signal-noise separation (SNS) applied to different measurement durations of rsfUS. The results showed that the SNS did not change when the measurement duration was increased to more than 210 s. Next, we measured short-duration rsfUS multi-slice measurements in the brain-wide area. The results showed that rsfUS with the short duration succeeded in detecting RSNs distributed in the brain-wide area consistent with RSNs detected by 11.7-T MRI under awake conditions (medial prefrontal cortex and cingulate cortex in the anterior DMN, retrosplenial cortex and visual cortex in the posterior DMN, somatosensory and motor cortexes in the lateral cortical network, thalamus, dorsal hippocampus, and medial cerebellum), confirming the reliability of the RSNs detected by rsfUS. However, bilateral RSNs located in the secondary somatosensory cortex, ventral hippocampus, auditory cortex, and lateral cerebellum extracted from rsfUS were different from the unilateral RSNs extracted from rsfMRI. These findings indicate the potential of rsfUS as a method for analyzing functional brain networks and should encourage future research to elucidate functional brain networks and their relationships with disease model mice.

A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice.

Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (µ)-electrocorticography (µECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped µECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current µECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel µECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the µECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the µECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our µECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.

Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models.

Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12 weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline.

Diffusion tensor imaging of oral carcinoma: Clinical evaluation and comparison with histopathological findings.

PURPOSE: This study aims to assess the usefulness of diffusion tensor imaging (DTI) as a noninvasive method for the evaluation of histological grade and lymph node metastasis in patients with oral carcinoma (OC). MATERIALS AND METHODS: Thirty-six consecutive patients with histologically confirmed OC underwent examination by 3-T MRI. DTI was performed using a single-shot echo-planar imaging sequence with b values of 0 and 1000 s/mm2 and motion-probing gradients in 12 noncollinear directions. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were compared with histopathological findings. The DTI parameters were correlated with the histological grade of the OCs based on the World Health Organization grading criteria and the presence or absence of lymph node metastasis. RESULTS: The FA values (0.275 ± 0.058) of OC were significantly lower than those of normal tongue, muscle, and parotid glands (P < 0.001 for all), and the MD, AD, and RD values (1.220 ± 0.149, 1.434 ± 0.172, and 1.019 ± 0.165 × 10-3 mm2/s, respectively) were significantly higher than their respective normal values (P < 0.001 for all). Significant inverse correlations with histological grades were shown for FA, MD, AD, and RD values in OC patients (r = -0.862, r = -0.797, r = -0.747, and r = -0.844, respectively; P < 0.001 for all). In addition, there was a significant difference in the FA values of metastatic and nonmetastatic lymph nodes (0.186 vs. 0.276), MD (0.923 vs. 1.242 × 10-3 mm2/s), AD (1.246 vs. 1.621 × 10-3 mm2/s), and RD (0.792 vs. 1.100 × 10-3 mm2/s; P < 0.001 for all). CONCLUSIONS: DTI may be clinically useful for the noninvasive evaluation of histological grade and lymph node metastasis in OC patients.

Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons.

The ability of animals to retrieve memories stored in response to the environment is essential for behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear. Here, we developed a novel chemogenetic activation strategy exploiting insect olfactory ionotropic receptors (IRs), termed "IR-mediated neuronal activation," and used it for selective stimulation of NE neurons in the locus coeruleus (LC). Drosophila melanogaster IR84a and IR8a subunits were expressed in LC NE neurons in transgenic mice. Application of phenylacetic acid (a specific ligand for the IR84a/IR8a complex) at appropriate doses induced excitatory responses of NE neurons expressing the receptors in both slice preparations and in vivo electrophysiological conditions, resulting in a marked increase of NE release in the LC nerve terminal regions (male and female). Ligand-induced activation of LC NE neurons enhanced the retrieval process of conditioned taste aversion without affecting taste sensitivity, general arousal state, and locomotor activity. This enhancing effect on taste memory retrieval was mediated, in part, through α1- and ß-adrenergic receptors in the basolateral nucleus of the amygdala (BLA; male). Pharmacological inhibition of LC NE neurons confirmed the facilitative role of these neurons in memory retrieval via adrenergic receptors in the BLA (male). Our findings indicate that the LC NE system, through projections to the BLA, controls the retrieval process of taste associative memory.SIGNIFICANCE STATEMENT Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation, but the role of the NE system in memory retrieval remains unclear. We developed a chemogenetic activation system based on insect olfactory ionotropic receptors and used it for selective stimulation of NE neurons in the locus coeruleus (LC) in transgenic mice. Ligand-induced activation of LC NE neurons enhanced the retrieval of conditioned taste aversion, which was mediated, in part, through adrenoceptors in the basolateral amygdala. Pharmacological blockade of LC activity confirmed the facilitative role of these neurons in memory retrieval. Our findings indicate that the LC-amygdala pathway plays an important role in the recall of taste associative memory.

Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations.

Baseline locomotion and behavioral traits in the common marmoset Parkinson's disease model were examined to provide basic information for preclinical evaluations of medical treatments. A single regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine at a cumulative dose of 5 mg/kg as the free base over three consecutive days was administered subcutaneously to 10 marmosets. Data obtained from these marmosets were compared to pre-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine levels or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine free marmosets. After the single regimen, reduced daily locomotion, a measure of immobility (a primary sign of Parkinsonism), was observed for more than a year. A moving tremor was also observed by visual inspection during this period. When apomorphine (0.13 mg/kg, s.c.) was administered, either right or left circling behavior was observed in a cylindrical chamber in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets, suggestive of unequal neural damage between the two brain hemispheres to different extents. MRI revealed that T1 relaxation time in the right substantia nigra correlated with right circling in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets. Histology was supportive of dopaminergic neural loss in the striatum. These results increase our understanding of the utility and limitations of the Parkinson's disease model in marmosets with a single 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine regimen, and provide reference data for efficacious preclinical evaluations.

Characteristic cerebral structural changes identified using voxel-based morphometry in patients with post-surgical chronic myelopathic pain.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Patients who undergo intramedullary spinal surgery occasionally experience post-surgical chronic pain; however, the underlying mechanisms are not yet completely understood. Therefore, this study aimed to identify the cerebral structural changes in patients with post-surgical chronic myelopathic pain using voxel-based morphometry. SETTING: Single university hospital in Tokyo, Japan. METHODS: Forty-nine patients who had undergone intramedullary spinal surgery between January 2002 and April 2014 participated in this study. Participants were classified into two groups based on their post-surgical chronic pain intensity: control (numeric rating scale score of <3) and pain (numeric rating scale score of ≥3) groups. We compared pain questionnaire and brain MRI between two groups. Brain MRI data of each participants was analyzed using voxel-based morphometry. RESULTS: Voxel-based morphometry revealed that the gray matter volume in the left supplementary motor area, left primary motor area, and left posterior cingulate cortex was higher in the pain group than that in the control group. In addition, the numeric rating scale score was significantly correlated with increased gray matter volume in the left primary motor area, left posterior cingulate cortex, and right superior parietal lobule. CONCLUSION: Present study elucidates the characteristic cerebral structural changes after an intramedullary spinal surgery using voxel-based morphometry and indicates that the structural changes in specific cerebral areas are associated with post-surgical chronic myelopathic pain.

Noninvasive technique to evaluate the muscle fiber characteristics using q-space imaging.

BACKGROUND: Skeletal muscles include fast and slow muscle fibers. The tibialis anterior muscle (TA) is mainly composed of fast muscle fibers, whereas the soleus muscle (SOL) is mainly composed of slow muscle fibers. However, a noninvasive approach for appropriately investigating the characteristics of muscles is not available. Monitoring of skeletal muscle characteristics can help in the evaluation of the effects of strength training and diseases on skeletal muscles. PURPOSE: The present study aimed to determine whether q-space imaging can distinguish between TA and SOL in in vivo mice. METHODS: In vivo magnetic resonance imaging of the right calves of mice (n = 8) was performed using a 7-Tesla magnetic resonance imaging system with a cryogenic probe. TA and SOL were assessed. q-space imaging was performed with a field of view of 10 mm × 10 mm, matrix of 48 × 48, and section thickness of 1000 µm. There were ten b-values ranging from 0 to 4244 s/mm2, and each b-value had diffusion encoding in three directions. Magnetic resonance imaging findings were compared with immunohistological findings. RESULTS: Full width at half maximum and Kurtosis maps of q-space imaging showed signal intensities consistent with immunohistological findings for both fast (myosin heavy chain II) and slow (myosin heavy chain I) muscle fibers. With regard to quantification, both full width at half maximum and Kurtosis could represent the immunohistological findings that the cell diameter of TA was larger than that of SOL (P < 0.01). CONCLUSION: q-space imaging could clearly differentiate TA from SOL using differences in cell diameters. This technique is a promising method to noninvasively estimate the fiber type ratio in skeletal muscles, and it can be further developed as an indicator of muscle characteristics.

Visualization of nerve fibers around the carotid bifurcation with use of a 9.4 Tesla microscopic magnetic resonance diffusion tensor imaging with tractography.

BACKGROUND: Precise imaging of nerves have been challenging in the head and neck region, mainly due to low spatial resolution. Here, we investigated how nerves in the head and neck region could be visualized using an ultra-high magnetic field MR system. METHODS: We used formol-carbol-fixed human cadaveric necks and obtained MR diffusion tensor images (DTIs) using a 9.4 Tesla (T) ultra-high magnetic field MR system. Afterward, we prepared tissue sections and checked the anatomic relationships between the neurons and the carotid artery in order to confirm that the visualized fibers are indeed neuron fibers. RESULTS: We were able to identify nerves, including the vagus nerve, the hypoglossal nerve, and the spinal-accessory nerve. Hematoxylin-eosin stained histological sections confirmed neuron fibers in the same anatomic position. CONCLUSION: This technique has the feasibility to be applied for a more accurate anatomic understanding, maybe even close to a histological level.

Oral carcinoma: Clinical evaluation using diffusion kurtosis imaging and its correlation with histopathologic findings.

PURPOSE: In this study, we aimed to determine the usefulness of diffusion kurtosis imaging (DKI) as a noninvasive method for evaluation of the histologic grade and lymph node metastasis in patients with oral carcinoma. MATERIALS AND METHODS: Twenty-seven patients with oral carcinoma were examined with a 3-T MR system and 16-channel coil. DKI data were obtained by a single-shot echo-planar imaging sequence with repetition time, 10,000 ms; echo time, 94 ms; field of view, 250 × 204.25 ms; matrix, 120 × 98; section thickness, 4 mm; four b values of 0, 500, 1000, and 2000 s/mm2; and motion-probing gradients in three orthogonal directions. Diffusivity (D) and kurtosis (K) were calculated using the equation: S = S0 ∙ exp(-b ∙ D + b2 ∙ D2 ∙ K/6). Conventional apparent diffusion coefficient (ADC) was also calculated. The MR images were compared with the histopathologic findings. RESULTS: Relative to the histologic grades (Grades 1, 2, and 3) of the 27 oral carcinomas, D values showed a significant inverse correlation (r = -0.885; P < 0.001) and K values showed a significant positive correlation (r = 0.869; P < 0.001), whereas ADC values showed no significant correlation (r = -0.311; P = 0.115). When comparing between metastatic and non-metastatic lymph nodes, significant differences in the D values (P < 0.001) and K values (P < 0.001), but not the ADC values (P = 0.110) became apparent. CONCLUSIONS: In patients with oral carcinoma, DKI seems to be clinically useful for the evaluation of histologic grades and lymph node metastasis.

Colorectal carcinoma: Ex vivo evaluation using q-space imaging; Correlation with histopathologic findings.

BACKGROUND: Although the prognosis of colorectal carcinoma (CRC) patients depends on the histologic grade (HG) and lymph node metastasis (LNM), accurate preoperative assessment of these prognostic factors is often difficult. PURPOSE: To assess the HG and extent of LNM by q-space imaging (QSI) for preoperative diagnosis of CRC. STUDY TYPE: Prospective. SPECIMEN: A total of 20 colorectal tissue samples containing adenocarcinomas and resected lymph nodes (LNs). FIELD STRENGTH/SEQUENCE: QSI was performed with a 3T MRI system using a diffusion-weighted echo-planar imaging sequence: repetition time, 10,000 msec; echo time, 216 or 210 msec; field of view, 113 × 73.45 mm; matrix, 120 × 78; section thickness, 4 mm; and 11 b values ranging from 0 to 9000 s/mm2 . ASSESSMENT: The mean displacement (MDP; µm), zero-displacement probability (ZDP; arbitrary unit [a.u.]), kurtosis (K; a.u.), and apparent diffusion coefficient (ADC) were analyzed by two observers and compared with histopathologic findings. STATISTICAL TESTS: Spearman's rank correlation coefficient, Mann-Whitney U-test, and ROC curve analyses. RESULTS: For all 20 carcinomas, the MDP, ZDP, K, and ADC were 8.87 ± 0.37 µm, 82.0 ± 6.2 a.u., 74.3 ± 3.0 a.u., and 0.219 ± 0.040 × 10-3 mm2 /s, respectively. The MDP (r = -0.768; P < 0.001), ZDP (r = 0.768; P < 0.001), and K (r = 0.785; P < 0.001) were significantly correlated with the HG of CRC, but not the ADC (r = 0.088; P = 0.712). There were also significant differences in the MDP, ZDP, and K between metastatic and nonmetastatic LNs (all, P < 0.001), but not the ADC (P = 0.082). In the HG of CRC and LNM, the area under the curve was significantly greater for MDP, ZDP, and K than for ADC. DATA CONCLUSION: QSI provides useful diagnostic information to assess the HG and extent of LNM in CRC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1059-1068.

The Brain/MINDS 3D digital marmoset brain atlas.

We present a new 3D digital brain atlas of the non-human primate, common marmoset monkey (Callithrix jacchus), with MRI and coregistered Nissl histology data. To the best of our knowledge this is the first comprehensive digital 3D brain atlas of the common marmoset having normalized multi-modal data, cortical and sub-cortical segmentation, and in a common file format (NIfTI). The atlas can be registered to new data, is useful for connectomics, functional studies, simulation and as a reference. The atlas was based on previously published work but we provide several critical improvements to make this release valuable for researchers. Nissl histology images were processed to remove illumination and shape artifacts and then normalized to the MRI data. Brain region segmentation is provided for both hemispheres. The data is in the NIfTI format making it easy to integrate into neuroscience pipelines, whereas the previous atlas was in an inaccessible file format. We also provide cortical, mid-cortical and white matter boundary segmentations useful for visualization and analysis.

Developmental trajectories of macroanatomical structures in common marmoset brain.

Morphometry studies of human brain development have revealed characteristics of some growth patterns, such as gray matter (GM) and white matter (WM), but the features that make human neurodevelopment distinct from that in other species remain unclear. Studies of the common marmoset (Callithrix jacchus), a small New World primate, can provide insights into unique features such as cooperative behaviors complementary to those from comparative analyses using mouse and rhesus monkey. In the present study, we analyzed developmental patterns of GM, WM, and cortical regions with volume measurements using longitudinal sample (23 marmosets; 11 male, 12 female) between the ages of one and 30months. Regional analysis using a total of 164 magnetic resonance imaging datasets revealed that GM volume increased before puberty (5.4months), but subsequently declined until adulthood, whereas WM volume increased rapidly before stabilizing around puberty (9.9months). Cortical regions showed similar patterns of increase and decrease, patterns with global GM but differed in the timing of volume peak and degree of decline across regions. The progressive-regressive pattern detected in both global and cortical GM was well correlated to phases of synaptogenesis and synaptic pruning reported in previous marmoset studies. A rapid increase in WM in early development may represent a distinctive aspect of human neurodevelopment. These findings suggest that studies of marmoset brain development can provide valuable comparative information that will facilitate a deeper understanding of human brain growth and neurodevelopmental disorders.

In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain.

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 µm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.