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Cortex; a Journal Devoted To the Study... Jan 2017Executive functions (EFs) are high-level cognitive processes, often associated with the frontal lobes, that control lower level processes in the service of goal-directed... (Review)
Review
Executive functions (EFs) are high-level cognitive processes, often associated with the frontal lobes, that control lower level processes in the service of goal-directed behavior. They include abilities such as response inhibition, interference control, working memory updating, and set shifting. EFs show a general pattern of shared but distinct functions, a pattern described as "unity and diversity". We review studies of EF unity and diversity at the behavioral and genetic levels, focusing on studies of normal individual differences and what they reveal about the functional organization of these cognitive abilities. In particular, we review evidence that across multiple ages and populations, commonly studied EFs (a) are robustly correlated but separable when measured with latent variables; (b) are not the same as general intelligence or g; (c) are highly heritable at the latent level and seemingly also highly polygenic; and (d) activate both common and specific neural areas and can be linked to individual differences in neural activation, volume, and connectivity. We highlight how considering individual differences at the behavioral and neural levels can add considerable insight to the investigation of the functional organization of the brain, and conclude with some key points about individual differences to consider when interpreting neuropsychological patterns of dissociation.
Topics: Brain; Cognition; Executive Function; Humans; Individuality; Memory, Short-Term; Neuropsychological Tests
PubMed: 27251123
DOI: 10.1016/j.cortex.2016.04.023 -
Genetics Oct 2020' behavioral states, like those of other animals, are shaped by its immediate environment, its past experiences, and by internal factors. We here review the literature... (Review)
Review
' behavioral states, like those of other animals, are shaped by its immediate environment, its past experiences, and by internal factors. We here review the literature on behavioral states and their regulation. We discuss dwelling and roaming, local and global search, mate finding, sleep, and the interaction between internal metabolic states and behavior.
Topics: Animals; Behavior, Animal; Caenorhabditis elegans; Energy Metabolism; Genetics, Behavioral; Sleep
PubMed: 33023930
DOI: 10.1534/genetics.120.303539 -
PLoS Genetics Feb 2019
Topics: Animals; Behavior, Animal; Female; Genetics, Behavioral; Humans; Male; Neurosciences; Research Design
PubMed: 30817793
DOI: 10.1371/journal.pgen.1008014 -
Current Opinion in Behavioral Sciences Apr 2015We describe the scientific enterprise at the intersection of evolutionary psychology and behavioral genetics-a field that could be termed -and how modern genetic data is...
We describe the scientific enterprise at the intersection of evolutionary psychology and behavioral genetics-a field that could be termed -and how modern genetic data is revolutionizing our ability to test questions in this field. We first explain how genetically informative data and designs can be used to investigate questions about the evolution of human behavior, and describe some of the findings arising from these approaches. Second, we explain how evolutionary theory can be applied to the investigation of behavioral genetic variation. We give examples of how new data and methods provide insight into the genetic architecture of behavioral variation and what this tells us about the evolutionary processes that acted on the underlying causal genetic variants.
PubMed: 25587556
DOI: 10.1016/j.cobeha.2014.09.005 -
Biological Psychiatry Jun 2021Emerging evidence points to a central role of mitochondria in psychiatric disorders. However, little is known about the molecular players that regulate mitochondria in...
BACKGROUND
Emerging evidence points to a central role of mitochondria in psychiatric disorders. However, little is known about the molecular players that regulate mitochondria in neural circuits regulating anxiety and depression and about how they impact neuronal structure and function. Here, we investigated the role of molecules involved in mitochondrial dynamics in medium spiny neurons (MSNs) from the nucleus accumbens (NAc), a hub of the brain's motivation system.
METHODS
We assessed how individual differences in anxiety-like (measured via the elevated plus maze and open field tests) and depression-like (measured via the forced swim and saccharin preference tests) behaviors in outbred rats relate to mitochondrial morphology (electron microscopy and 3-dimensional reconstructions) and function (mitochondrial respirometry). Mitochondrial molecules were measured for protein (Western blot) and messenger RNA (quantitative reverse transcriptase polymerase chain reaction, RNAscope) content. Dendritic arborization (Golgi Sholl analyses), spine morphology, and MSN excitatory inputs (patch-clamp electrophysiology) were characterized. MFN2 overexpression in the NAc was induced through an AAV9-syn1-MFN2.
RESULTS
Highly anxious animals showed increased depression-like behaviors, as well as reduced expression of the mitochondrial GTPase MFN2 in the NAc. They also showed alterations in mitochondria (i.e., respiration, volume, and interactions with the endoplasmic reticulum) and MSNs (i.e., dendritic complexity, spine density and typology, and excitatory inputs). Viral MFN2 overexpression in the NAc reversed all of these behavioral, mitochondrial, and neuronal phenotypes.
CONCLUSIONS
Our results implicate a causal role for accumbal MFN2 on the regulation of anxiety and depression-like behaviors through actions on mitochondrial and MSN structure and function. MFN2 is posited as a promising therapeutic target to treat anxiety and associated behavioral disturbances.
Topics: Animals; Anxiety; Depression; Mice; Mice, Inbred C57BL; Mitochondria; Neurons; Nucleus Accumbens; Rats
PubMed: 33583561
DOI: 10.1016/j.biopsych.2020.12.003 -
Experimental Neurology Jan 2018Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology is complex, with several genetic factors likely to be involved as well as environmental... (Review)
Review
Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology is complex, with several genetic factors likely to be involved as well as environmental factors. Immune dysregulation has gained significant attention as a causal mechanism in ASD pathogenesis. ASD has been associated with immune abnormalities in the brain and periphery, including inflammatory disorders and autoimmunity in not only the affected individuals but also their mothers. Prenatal exposure to maternal immune activation (MIA) has been implicated as an environmental risk factor for ASD. In support of this notion, animal models have shown that MIA results in offspring with behavioral, neurological, and immunological abnormalities similar to those observed in ASD. This raises the question of how MIA exposure can lead to ASD in susceptible individuals. Recent evidence points to a potential inflammation pathway linking MIA-associated ASD with the activity of T helper 17 (Th17) lymphocytes and their effector cytokine interleukin-17A (IL-17A). IL-17A has been implicated from human studies and elevated IL-17A levels in the blood have been found to correlate with phenotypic severity in a subset of ASD individuals. In MIA model mice, elevated IL-17A levels also have been observed. Additionally, antibody blockade to inhibit IL-17A signaling was found to prevent ASD-like behaviors in offspring exposed to MIA. Therefore, IL-17A dysregulation may play a causal role in the development of ASD. The source of increased IL-17A in the MIA mouse model was attributed to maternal Th17 cells because genetic removal of the transcription factor RORγt to selectively inhibit Th17 differentiation in pregnant mice was able to prevent ASD-like behaviors in the offspring. Similar to ASD individuals, the MIA-exposed offspring also displayed cortical dysplasia which could be prevented by inhibition of IL-17A signaling in pregnant mice. This finding reveals one possible cellular mechanism through which ASD-related cognitive and behavioral deficits may emerge following maternal inflammation. IL-17A can exert strong effects on cell survival and differentiation and the activity of signal transduction cascades, which can have important consequences during cortical development on neural function. This review examines IL-17A signaling pathways in the context of both immunity and neural function that may contribute to the development of ASD associated with MIA.
Topics: Adult; Animals; Autism Spectrum Disorder; Female; Humans; Infant, Newborn; Interleukin-17; Mice; Pregnancy
PubMed: 28455196
DOI: 10.1016/j.expneurol.2017.04.010 -
Genes, Brain, and Behavior Mar 2020Alcohol use disorders (AUDs) lead to early death and many devastating consequences for individuals, families and society. Currently, few effective treatments are... (Review)
Review
Alcohol use disorders (AUDs) lead to early death and many devastating consequences for individuals, families and society. Currently, few effective treatments are available, but emerging research suggests exercise might be beneficial in some individuals. To develop the most effective exercise treatment program, more research on intensity, type, timing, stage of addiction, drug involved, sex of subject and subject population is needed. This review highlights the complexity of the interaction between alcohol behaviors and exercise, with a focus on the role of sex and genetics. Moreover, we describe a variety of rodent models used to investigate the neuronal physiology changes that underlie alcohol consumption and exercise. Specifically, current data indicate that moderate exercise may ameliorate neuronal damage caused by alcohol consumption. Additionally, we describe studies of rodent models in the context of hedonic substitution to draw broad conclusions about shared underlying neurobiological mechanisms. Until recently, most studies in rodents were performed only in males, and few studies have utilized different genetic strains of mice or rats. Comparing similar behavioral paradigms across sex and strain, it has become clear that major sex and genetic differences exist for each behavioral context alone (alcohol consumption and exercise) and combined. Therefore, future research in this area should be developed with careful study design and attention to address both of these factors.
Topics: Alcoholism; Animals; Exercise; Female; Genotype; Humans; Male; Neurons; Sex Factors
PubMed: 31912976
DOI: 10.1111/gbb.12632 -
Genetics Apr 2018Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including... (Review)
Review
Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The "motor" of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the "drivers" of the sleep motor: arousal inhibits "sleep-active" neurons whereas various sleep-promoting "tiredness" pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems.
Topics: Animals; Biological Evolution; Humans; Mammals; Models, Animal; Neurons; Sleep
PubMed: 29618588
DOI: 10.1534/genetics.117.300521 -
Proceedings of the National Academy of... Jul 2022The question of the heritability of behavior has been of long fascination to scientists and the broader public. It is now widely accepted that most behavioral variation...
The question of the heritability of behavior has been of long fascination to scientists and the broader public. It is now widely accepted that most behavioral variation has a genetic component, although the degree of genetic influence differs widely across behaviors. Starting with Mendel's remarkable discovery of "inheritance factors," it has become increasingly clear that specific genetic variants that influence behavior can be identified. This goal is not without its challenges: Unlike pea morphology, most natural behavioral variation has a complex genetic architecture. However, we can now apply powerful genome-wide approaches to connect variation in DNA to variation in behavior as well as analyses of behaviorally related variation in brain gene expression, which together have provided insights into both the genetic mechanisms underlying behavior and the dynamic relationship between genes and behavior, respectively, in a wide range of species and for a diversity of behaviors. Here, we focus on two systems to illustrate both of these approaches: the genetic basis of burrowing in deer mice and transcriptomic analyses of division of labor in honey bees. Finally, we discuss the troubled relationship between the field of behavioral genetics and eugenics, which reminds us that we must be cautious about how we discuss and contextualize the connections between genes and behavior, especially in humans.
Topics: Animals; Bees; Genetics, Behavioral; Genomics; Heredity; Humans; Inheritance Patterns; Mice; Pisum sativum
PubMed: 35858398
DOI: 10.1073/pnas.2122154119 -
Genes, Brain, and Behavior Feb 2020The field of behavioral genetics has recently begun to explore the effect of age on social behaviors. Such studies are particularly important, as certain... (Review)
Review
The field of behavioral genetics has recently begun to explore the effect of age on social behaviors. Such studies are particularly important, as certain neuropsychiatric disorders with abnormal social interactions, like autism and schizophrenia, have been linked to older parents. Appropriate social interaction can also have a positive impact on longevity, and is associated with successful aging in humans. Currently, there are few genetic models for understanding the effect of aging on social behavior and its potential transgenerational inheritance. The fly is emerging as a powerful model for identifying the basic molecular mechanisms underlying neurological and neuropsychiatric disorders. In this review, we discuss these recent advancements, with a focus on how studies in Drosophila melanogaster have provided insight into the effect of aging on aspects of social behavior, including across generations.
Topics: Aging; Animals; Behavior, Animal; Courtship; Drosophila melanogaster; Female; Genetics, Behavioral; Interpersonal Relations; Male; Models, Animal; Sexual Behavior, Animal; Social Behavior
PubMed: 31286644
DOI: 10.1111/gbb.12598