Combining animal personalities with transcriptomics resolves individual variation within a wild-type zebrafish population and identifies underpinning molecular differences in brain function

The field of animal behavior has experienced a surge of studies focusing on functional differences among individuals in their behavioral tendencies (‘animal personalities’) and the relationships between different axes of behavioral variation (‘behavioral syndromes’). Many important developments in this field have arisen through research using insects and other terrestrial arthropods, in part, because they present the opportunity to test hypotheses not accessible in other taxa. This chapter reviews how studies on insects and spiders have advanced the study of animal personalities by describing the mechanisms underlying the emergence of individual variation and their ecological consequences. Furthermore, studies accounting for animal personalities can expand our understanding of phenomena in insect science like metamorphosis, eusociality, and applied insect behavior. In addition, this chapter serves to highlight some of the most exciting issues at the forefront of our field and to inspire entomologists and behaviorists alike to seek the answers to these questions.

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Assessing Variations in Areal Organization for the Intrinsic Brain: From Fingerprints to Reliability

10.1101/035790 ◽

2016 ◽

Cited By ~ 3

Author(s):

Ting Xu ◽

Alexander Opitz ◽

R. Cameron Craddock ◽

Margaret Wright ◽

Xi-Nian Zuo ◽

...

Keyword(s):

Individual Variation ◽

Brain Function ◽

Intraclass Correlation ◽

Resting State Fmri ◽

Single Individual ◽

Initial Application ◽

Novel Approach ◽

Gradient Based ◽

Healthy Participants

AbstractResting state fMRI (R-fMRI) is a powerful in-vivo tool for examining the functional architecture of the human brain. Recent studies have demonstrated the ability to characterize transitions between functionally distinct cortical areas through the mapping of gradients in intrinsic functional connectivity (iFC) profiles. To date, this novel approach has primarily been applied to iFC profiles averaged across groups of individuals, or in one case, a single individual scanned multiple times. Here, we used a publically available R-fMRI dataset, in which 30 healthy participants were scanned 10 times (10 minutes per session), to investigate differences in full-brain transition profiles (i.e., gradient maps, edge maps) across individuals, and their reliability. 10-minute R-fMRI scans were sufficient to achieve high accuracies in efforts to “fingerprint” individuals based upon full-brain transition profiles. Regarding testretest reliability, the image-wise intraclass correlation coefficient (ICC) was moderate, and vertex-level ICC varied depending on region; larger durations of data yielded higher reliability scores universally. Initial application of gradient-based methodologies to a recently published dataset obtained from twins suggested inter-individual variation in areal profiles might have genetic and familial origins. Overall, these results illustrate the utility of gradient-based iFC approaches for studying inter-individual variation in brain function.

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Imaging Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism

10.1101/450973 ◽

2018 ◽

Cited By ~ 1

Author(s):

Eylan Yutuc ◽

Roberto Angelini ◽

Mark Baumert ◽

Natalia Mast ◽

Irina Pikuleva ◽

...

Keyword(s):

Mass Spectrometry ◽

Mouse Brain ◽

Brain Function ◽

Mass Spectrometry Imaging ◽

Cholesterol Metabolism ◽

Biologically Active ◽

Wild Type ◽

Tissue Slices ◽

The Brain

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

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Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants

Genes ◽

10.3390/genes11091021 ◽

2020 ◽

Vol 11 (9) ◽

pp. 1021

Author(s):

Amjad Khan ◽

Zhichao Miao ◽

Muhammad Umair ◽

Amir Ullah ◽

Mohammad A. Alshabeeb ◽

...

Keyword(s):

Intellectual Disability ◽

Secondary Structure ◽

Homology Modeling ◽

Exome Sequencing ◽

In Silico ◽

Brain Function ◽

Sanger Sequencing ◽

Autosomal Recessive ◽

Wild Type ◽

Genetic Condition

Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.

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Awake functional MRI detects neural circuit dysfunction in a mouse model of autism

Science Advances ◽

10.1126/sciadv.aav4520 ◽

2020 ◽

Vol 6 (6) ◽

pp. eaav4520 ◽

Cited By ~ 8

Author(s):

Tomokazu Tsurugizawa ◽

Kota Tamada ◽

Nobukazu Ono ◽

Sachise Karakawa ◽

Yuko Kodama ◽

...

Keyword(s):

Functional Mri ◽

Brain Function ◽

Copy Number ◽

Diffusion Mri ◽

Neural Circuit ◽

Ex Vivo ◽

Disease Model ◽

Wild Type ◽

Number Variation ◽

Translational Approach

MRI has potential as a translational approach from rodents to humans. However, given that mouse functional MRI (fMRI) uses anesthetics for suppression of motion, it has been difficult to directly compare the result of fMRI in “unconsciousness” disease model mice with that in “consciousness” patients. We develop awake fMRI to investigate brain function in 15q dup mice, a copy number variation model of autism. Compared to wild-type mice, we find that 15q dup is associated with whole-brain functional hypoconnectivity and diminished fMRI responses to odors of stranger mice. Ex vivo diffusion MRI reveals widespread anomalies in white matter ultrastructure in 15q dup mice, suggesting a putative anatomical substrate for these functional hypoconnectivity. We show that d-cycloserine (DCS) treatment partially normalizes these anormalies in the frontal cortex of 15q dup mice and rescues some social behaviors. Our results demonstrate the utility of awake rodent fMRI and provide a rationale for further investigation of DCS therapy.

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Individual differences in aggressive and peaceful behavior: new insights and future directions

Behaviour ◽

10.1163/1568539x-00003400 ◽

2016 ◽

Vol 153 (9-11) ◽

pp. 1139-1169 ◽

Cited By ~ 2

Author(s):

Christine E. Webb ◽

Peter Verbeek

Keyword(s):

Biological Sciences ◽

Individual Differences ◽

Individual Variation ◽

Social Systems ◽

Personality Research ◽

Social Species ◽

Post Conflict ◽

Variation Patterns ◽

Animal Personalities ◽

Future Work

Consistent individual differences in animal behaviour are an increasingly common focus of research across various behavioural and biological sciences. Such ‘animal personalities’ comprise a diverse repertoire of behavioural tendencies, recently expanding to incorporate the social domain. Aggression and peace, hallmarks of many social systems including that of humans, warrant integration with this literature. Specifically, animal personality research should consider the potential role of stable conflict and post-conflict behavioural tendencies. We focus our discussion primarily on examples in nonhuman primates and humans, but suggest that individual variation patterns are relevant for any social species in which these phenomena exist. In highly gregarious species, an individual’s conflict and post-conflict tendencies can affect the strength and stability of its social bonds. Because social relationships in turn impact survival and reproductive success, we also encourage future work to investigate the ultimate (i.e., fitness-relevant) consequences of individual variation in aggressive and peaceful behaviour.

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Concordance among indices of intrinsic brain function: Insights from inter-individual variation and temporal dynamics

Science Bulletin ◽

10.1016/j.scib.2017.09.015 ◽

2017 ◽

Vol 62 (23) ◽

pp. 1572-1584 ◽

Cited By ~ 31

Author(s):

Chao-Gan Yan ◽

Zhen Yang ◽

Stanley J. Colcombe ◽

Xi-Nian Zuo ◽

Michael P. Milham

Keyword(s):

Individual Variation ◽

Brain Function ◽

Temporal Dynamics

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Concordance Among Indices of Intrinsic Brain Function: Insights from Inter-Individual Variation and Temporal Dynamics

10.1101/048405 ◽

2016 ◽

Author(s):

Chao-Gan Yan ◽

Zhen Yang ◽

Stanley J. Colcombe ◽

Xi-Nian Zuo ◽

Michael P. Milham

Keyword(s):

Individual Variation ◽

Brain Function ◽

Temporal Dynamics ◽

Brain Activity ◽

Low Frequency ◽

Resting State Fmri ◽

Surrogate Data ◽

Linear Increase ◽

Intrinsic Brain Activity ◽

High Degree

ABSTRACTVarious resting-state fMRI (R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the common and unique aspects these indices capture. The present work provided a comprehensive examination of inter-individual variation and intra-individual temporal variation for commonly used measures, including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, network centrality and global signal correlation. Regardless of whether examining intra-individual or inter-individual variation, we found that these definitionally distinct R-fMRI indices tend to exhibit a relatively high degree of covariation, which doesn’t exist in phase randomized surrogate data. As a measure of intrinsic brain function, concordance for R-fMRI indices was negatively correlated with age across individuals (i.e., concordance among functional indices decreased with age). To understand the functional significance of concordance, we noted that higher concordance was generally associated with higher strengths of R-fMRI indices, regardless of whether looking through the lens of inter-individual (i.e., high vs. low concordance participants) or intra-individual (i.e., high vs. low concordance states identified via temporal dynamic analyses) differences. We also noted a linear increase in functional concordance together with the R-fMRI indices through the scan, which may suggest a decrease in arousal. The current study demonstrated an enriched picture regarding the relationship among the R-fMRI indices, as well as provided new insights in examining dynamic states within and between individuals.

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Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices

Journal of Neurophysiology ◽

10.1152/jn.00890.2015 ◽

2016 ◽

Vol 115 (3) ◽

pp. 1263-1272 ◽

Cited By ~ 21

Author(s):

Min-Yu Sun ◽

Yukitoshi Izumi ◽

Ann Benz ◽

Charles F. Zorumski ◽

Steven Mennerick

Keyword(s):

Brain Function ◽

Ex Vivo ◽

Hippocampal Slices ◽

Treatment Strategies ◽

Glucose Deprivation ◽

Wild Type ◽

Drug Candidates ◽

Excitatory Transmission ◽

The Central Nervous System ◽

New Treatment

N-methyl-d-aspartate receptors (NMDARs), a major subtype of glutamate receptors mediating excitatory transmission throughout the central nervous system (CNS), play critical roles in governing brain function and cognition. Because NMDAR dysfunction contributes to the etiology of neurological and psychiatric disorders including stroke and schizophrenia, NMDAR modulators are potential drug candidates. Our group recently demonstrated that the major brain cholesterol metabolite, 24 S-hydroxycholesterol (24S-HC), positively modulates NMDARs when exogenously administered. Here, we studied whether endogenous 24S-HC regulates NMDAR activity in hippocampal slices. In CYP46A1−/−(knockout; KO) slices where endogenous 24S-HC is greatly reduced, NMDAR tone, measured as NMDAR-to-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory postsynaptic current (EPSC) ratio, was reduced. This difference translated into more NMDAR-driven spiking in wild-type (WT) slices compared with KO slices. Application of SGE-301, a 24S-HC analog, had comparable potentiating effects on NMDAR EPSCs in both WT and KO slices, suggesting that endogenous 24S-HC does not saturate its NMDAR modulatory site in ex vivo slices. KO slices did not differ from WT slices in either spontaneous neurotransmission or in neuronal intrinsic excitability, and exhibited LTP indistinguishable from WT slices. However, KO slices exhibited higher resistance to persistent NMDAR-dependent depression of synaptic transmission induced by oxygen-glucose deprivation (OGD), an effect restored by SGE-301. Together, our results suggest that loss of positive NMDAR tone does not elicit compensatory changes in excitability or transmission, but it protects transmission against NMDAR-mediated dysfunction. We expect that manipulating this endogenous NMDAR modulator may offer new treatment strategies for neuropsychiatric dysfunction.

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Human phenylethanolamineN-methyltransferase genetic polymorphisms and exercise-induced epinephrine release

Physiological Genomics ◽

10.1152/physiolgenomics.00248.2007 ◽

2008 ◽

Vol 33 (3) ◽

pp. 323-332 ◽

Cited By ~ 6

Author(s):

Yuan Ji ◽

Eric M. Snyder ◽

Brooke L. Fridley ◽

Oreste E. Salavaggione ◽

Irene Moon ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Individual Variation ◽

Wild Type ◽

Nucleotide Polymorphism ◽

Mobility Shift ◽

Caucasian American ◽

Single Nucleotide ◽

First Intron ◽

Exercise Induced ◽

Different Levels

Phenylethanolamine N-methyltransferase (PNMT) catalyzes the synthesis of epinephrine from norepinephrine. We previously identified and functionally characterized common sequence variation in the PNMT gene. In the present study, we set out to determine whether common PNMT genetic polymorphisms might be associated with individual variation in circulating epinephrine levels during exercise in 74 Caucasian American subjects. Circulating epinephrine levels were measured in each subject at baseline and during two different levels of exercise, ∼40% and ∼75% of peak workload. The PNMT gene was resequenced with DNA from each study subject. Eight novel PNMT polymorphisms were identified, including a C319T (Arg107Cys) nonsynonymous single nucleotide polymorphism (SNP) and I1G(280)A, a SNP located in the first intron of the gene. The I1G(280)A SNP was significantly associated with decreased exercise-induced circulating epinephrine levels and with a decreased epinephrine-to-norepinephrine ratio. The Cys107 recombinant allozyme displayed significantly lower levels of both PNMT activity and immunoreactive protein than the wild-type allozyme after transfection into COS-1 cells, but it did not appear to be associated with level of epinephrine in these subjects. Electrophoretic mobility shift and reporter gene assays performed with the I1G(280)A SNP indicated that this polymorphism could bind nuclear proteins and might modulate gene transcription. Our studies suggest that functionally significant variant sequence in the human PNMT gene might contribute to individual variation in levels of circulating epinephrine during exercise.

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