Oxytocin, Neural Plasticity, and Social Behavior

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Robert C. Froemke ◽  
Larry J. Young
Keyword(s):  
Social Behavior ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
Social Behaviors ◽  
Neuron Activity ◽  
Annual Review ◽  
Publication Date ◽  
Social Stimuli ◽  
Circuit Function

Oxytocin regulates parturition, lactation, parental nurturing, and many other social behaviors in both sexes. The circuit mechanisms by which oxytocin modulates social behavior are receiving increasing attention. Here, we review recent studies on oxytocin modulation of neural circuit function and social behavior, largely enabled by new methods of monitoring and manipulating oxytocin or oxytocin receptor neurons in vivo. These studies indicate that oxytocin can enhance the salience of social stimuli and increase signal-to-noise ratios by modulating spiking and synaptic plasticity in the context of circuits and networks. We highlight oxytocin effects on social behavior in nontraditional organisms such as prairie voles and discuss opportunities to enhance the utility of these organisms for studying circuit-level modulation of social behaviors. We then discuss recent insights into oxytocin neuron activity during social interactions. We conclude by discussing some of the major questions and opportunities in the field ahead. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

In Vivo Dynamics of the Latent Reservoir for HIV-1: New Insights and Implications for Cure

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Janet D. Siliciano ◽  
Robert F. Siliciano
Keyword(s):  
Limit Of Detection ◽  
Latent Reservoir ◽  
Annual Review ◽  
Publication Date ◽  
Viral Rebound ◽  
Major Barrier ◽  
Persons Living With Hiv ◽  
Recent Developments ◽  
Hiv 1

Although antiretroviral therapy (ART) can reduce viremia to below the limit of detection and allow persons living with HIV-1 (PLWH) to lead relatively normal lives, viremia rebounds when treatment is interrupted. Rebound reflects viral persistence in a stable latent reservoir in resting CD4+ T cells. This reservoir is now recognized as the major barrier to cure and is the focus of intense international research efforts. Strategies to cure HIV-1 infection include interventions to eliminate this reservoir, to prevent viral rebound from the reservoir, or to enhance immune responses such that viral replication is effectively controlled. Here we consider recent developments in understanding the composition of the reservoir and how it can be measured in clinical studies. We also discuss exciting new insights into the in vivo dynamics of the reservoir and the reasons for its remarkable stability. Finally we discuss recent discoveries on the complex processes that govern viral rebound. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Compositional, Structural, and Kinetic Aspects of Lipid Digestion and Bioavailability: In Vitro, In Vivo, and Modeling Approaches

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Sébastien Marze
Keyword(s):  
Annual Review ◽  
Publication Date ◽  
Lipid Digestion ◽  
Modeling Approaches ◽  
Digestion Kinetics ◽  
Food Design ◽  
Structural Aspects ◽  
Development And Evolution

Lipid digestion and bioavailability are usually investigated separately, using different approaches (in vitro, modeling, in vivo). However, a few inclusive studies show that their kinetics are closely linked. Lipid bioavailability kinetics is likely involved in the development and evolution of several diseases, so lipid digestion kinetics could be involved as well and can be modulated by food design or combination. To illustrate this possibility, the compositional and structural aspects of lipid digestion kinetics, as investigated using in vitro and modeling approaches, are presented first. Then, in vivo and mixed approaches enabling the study of both kinetics are reviewed and discussed. Finally, disparate modeling approaches are introduced, and a unifying modeling scheme is proposed, opening new perspectives for understanding the role and interactions of various factors (chemical, physical, and biological) involved in lipid metabolism. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Richard Hakim ◽  
Kiarash Shamardani ◽  
Hillel Adesnik
Keyword(s):  
Visual Cortex ◽  
Neural Circuit ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Gamma Band ◽  
Neuron Activity ◽  
Mouse Visual Cortex ◽  
Retinotopic Map

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex.

scholarly journals Physiologically Based Modeling of Food Digestion and Intestinal Microbiota: State of the Art and Future Challenges. An INFOGEST Review

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Steven Le Feunteun ◽  
Ahmed Al-Razaz ◽  
Matthijs Dekker ◽  
Erwin George ◽  
Beatrice Laroche ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Historical Background ◽  
Annual Review ◽  
Publication Date ◽  
Physiologically Based ◽  
The Future ◽  
Future Challenges ◽  
Full Picture ◽  
Food Digestion

This review focuses on modeling methodologies of the gastrointestinal tract during digestion that have adopted a systems-view approach and, more particularly, on physiologically based compartmental models of food digestion and host–diet–microbiota interactions. This type of modeling appears very promising for integrating the complex stream of mechanisms that must be considered and retrieving a full picture of the digestion process from mouth to colon. We may expect these approaches to become more and more accurate in the future and to serve as a useful means of understanding the physicochemical processes occurring in the gastrointestinal tract, interpreting postprandial in vivo data, making relevant predictions, and designing healthier foods. This review intends to provide a scientific and historical background of this field of research, before discussing the future challenges and potential benefits of the establishment of such a model to study and predict food digestion and absorption in humans. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Germline Nuclear-predominant Pten Murine Model Exhibits Impaired Social and Perseverative Behavior, Microglial Activation, and Increased Oxytocinergic Activity

2020 ◽  
Author(s):  
Nick Sarn ◽  
Stetson Thacker ◽  
Hyunpil Lee ◽  
Charis Eng
Keyword(s):  
Social Behavior ◽  
Microglial Activation ◽  
Suppressor Gene ◽  
Social Impairment ◽  
Social Stimuli ◽  
Animal Modeling ◽  
Therapeutic Modalities ◽  
Downstream Effects

Abstract BackgroundAutism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity, cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes.MethodsTo understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant PtenY68H/+ mouse. We subjected the PtenY68H/+ mouse to morphological and behavioral phenotyping, including the three-chamber sociability and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the PtenY68H/+ cortex, which profiled gene expression.ResultsDespite no significant changes in downstream canonical Pten signaling, we found that the PtenY68H/+ mouse presents with macrocephaly, social impairment (i.e., decreased sociability, decreased preference for novel social stimuli, and increased perseverative activity), with significant microglial activation accompanied by enhanced phagocytosis. Because of lack of canonical signaling alterations, we turned to analyzing the neural transcriptomes, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was 5-fold overexpressed (P = 0.0018) and oxytocin protein was strongly overexpressed in the PtenY68H/+ hypothalamus. ConclusionsThe nuclear-predominant PtenY68H/+ model has clarified that Pten dysfunction links to microglial pathology and that timed decreased in Pten levels is the provoking insult. Notably, we demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD.

scholarly journals Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

2016 ◽  
Author(s):  
Cian O’Donnell ◽  
J. Tiago Gonçalves ◽  
Carlos Portera-Cailliau ◽  
Terrence J. Sejnowski
Keyword(s):  
Neural Circuit ◽  
Fragile X ◽  
Brain Disorders ◽  
Imaging Data ◽  
Neural Firing ◽  
Knock Out ◽  
Brain Circuitry ◽  
Circuit Function ◽  
Cellular Components

AbstractA leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this onedimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here we combined computational simulations with analysis of in vivo 2-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: 1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; 2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; 3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher-dimensional models that can better capture the multidimensional computational functions of neural circuits.

scholarly journals Nanomechanics of Blood Clot and Thrombus Formation

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Marco M. Domingues ◽  
Filomena A. Carvalho ◽  
Nuno C. Santos
Keyword(s):  
Mechanical Properties ◽  
Thrombus Formation ◽  
Blood Clot ◽  
Fibrin Clot ◽  
Annual Review ◽  
Publication Date ◽  
New Methods ◽  
Fibrin Network ◽  
Protein Cell

Mechanical properties have been extensively studied in pure elastic or viscous materials; however, most biomaterials possess both physical properties in a viscoelastic component. How the biomechanics of a fibrin clot is related to its composition and the microenvironment where it is formed is not yet fully understood. This review gives an outline of the building mechanisms for blood clot mechanical properties and how they relate to clot function. The formation of a blood clot in health conditions or the formation of a dangerous thrombus go beyond the mere polymerization of fibrinogen into a fibrin network. The complex composition and localization of in vivo fibrin clots demonstrate the interplay between fibrin and/or fibrinogen and blood cells. Studying these protein–cell interactions and clot mechanical properties may represent new methods for the evaluation of cardiovascular diseases (the leading cause of death worldwide), creating new possibilities for clinical diagnosis, prognosis, and therapy. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Cian O'Donnell ◽  
J Tiago Gonçalves ◽  
Carlos Portera-Cailliau ◽  
Terrence J Sejnowski
Keyword(s):  
Neural Circuit ◽  
Fragile X ◽  
Brain Disorders ◽  
Imaging Data ◽  
Neural Firing ◽  
Knock Out ◽  
Brain Circuitry ◽  
Circuit Function ◽  
Cellular Components

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.

Brain–Machine Interfaces: Closed-Loop Control in an Adaptive System

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ethan Sorrell ◽  
Michael E. Rule ◽  
Timothy O’Leary
Keyword(s):  
Neural Plasticity ◽  
Closed Loop ◽  
Neural Code ◽  
Annual Review ◽  
Publication Date ◽  
Closed Loop Control ◽  
Brain Machine Interfaces ◽  
Ongoing Research ◽  
Loop Control ◽  
The Impact

Brain–machine interfaces (BMIs) promise to restore movement and communication in people with paralysis and ultimately allow the human brain to interact seamlessly with external devices, paving the way for a new wave of medical and consumer technology. However, neural activity can adapt and change over time, presenting a substantial challenge for reliable BMI implementation. Large-scale recordings in animal studies now allow us to study how behavioral information is distributed in multiple brain areas, and state-of-the-art interfaces now incorporate models of the brain as a feedback controller. Ongoing research aims to understand the impact of neural plasticity on BMIs and find ways to leverage learning while accommodating unexpected changes in the neural code. We review the current state of experimental and clinical BMI research, focusing on what we know about the neural code, methods for optimizing decoders for closed-loop control, and emerging strategies for addressing neural plasticity. Expected final online publication date for the Annual Review of Control, Robotics, and Autonomous Systems, Volume 4 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals BACE inhibition-dependent repair of Alzheimer’s pathophysiology

2017 ◽  
Vol 114 (32) ◽  
pp. 8631-8636 ◽  
Author(s):  
Aylin D. Keskin ◽  
Maja Kekuš ◽  
Helmuth Adelsberger ◽  
Ulf Neumann ◽  
Derya R. Shimshek ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Cognitive Impairments ◽  
Amyloid Β ◽  
Pathogenic Role ◽  
Memory Impairments ◽  
Wide Range ◽  
Key Enzyme ◽  
Potential Benefits ◽  
Circuit Function

Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear. Using histochemistry, in vivo Ca2+ imaging, and behavioral analyses in a mouse model of AD, we demonstrate that along with reducing prefibrillary Aβ surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaired long-range circuit function, and memory defects. The functional neuronal impairments reappeared after infusion of soluble Aβ, mechanistically linking Aβ pathology to neuronal and cognitive dysfunction. These data highlight the potential benefits of BACE inhibition for the effective treatment of a wide range of AD-like pathophysiological and cognitive impairments.

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