scholarly journals Wiring diagram of the oxytocin system in the mouse brain

2020 ◽  
Author(s):  
Seoyoung Son ◽  
Steffy B. Manjila ◽  
Kyra T. Newmaster ◽  
Yuan-ting Wu ◽  
Daniel J. Vanselow ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Physiological Responses ◽  
Brain Regions ◽  
Receptor Expression ◽  
Wiring Diagram ◽  
Whole Brain ◽  
Functional Studies ◽  
Quantitative Correlation ◽  
Anatomical Arrangement ◽  
The Brain

AbstractIn the brain, oxytocin (OT) neurons make direct connections with discreet regions to regulate social behavior and diverse physiological responses. Obtaining an integrated neuroanatomical understanding of pleiotropic OT functions requires comprehensive wiring diagram of OT neurons. Here, we have created a whole-brain map of distribution and anatomical connections of hypothalamic OT neurons, and their relationship with OT receptor (OTR) expression. We used our brain-wide quantitative mapping at cellular resolution combined with a 2D flatmap to provide an intuitive understanding of the spatial arrangements of OT neurons. Then, we utilized knock-in Ot-Cre mice injected with Cre dependent retrograde monosynaptic rabies viruses and anterograde adeno associated virus to interrogate input-output patterns. We find that brain regions with cognitive functions such as the thalamus are reciprocally connected, while areas associated with physiological functions such as the hindbrain receive unidirectional outputs. Lastly, comparison between OT output and OTR expression showed no significant quantitative correlation, suggesting that OT transmission mostly occurs through indirect pathways. In summary, our OT wiring diagram provides structural and quantitative insights of distinct behavioral functions of OT neurons in the brain.Significance StatementOxytocin (OT) neurons in the brain play an important role in socio-physiological responses. Impairment of OT signaling has been implicated in many neurodevelopmental disorders. To understand diverse OT functions in the context of discreet neural circuits, it is imperative to understand the anatomical arrangement of OT neurons across the whole brain in significant detail. Here, we have established a comprehensive brain-wide wiring diagram of OT neurons. Our anatomical and connectivity map of OT neurons includes brain-wide cell distribution, synaptic inputs, axonal outputs, and their relationships with the oxytocin receptor expression. This whole brain structural perspective of the OT system provides a foundation for understanding the diversity of neural circuits modulated by OT and will guide future circuit-based OT functional studies.

scholarly journals Increased sensitivity to strong perturbations in a whole-brain model of LSD

2021 ◽  
Author(s):  
Beatrice M. Jobst ◽  
Selen Atasoy ◽  
Adrián Ponce-Alvarez ◽  
Ana Sanjuán ◽  
Leor Roseman ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
External Perturbation ◽  
Brain Regions ◽  
Lysergic Acid ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Whole Brain ◽  
Response Diversity ◽  
Brain States ◽  
The Brain

AbstractLysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain’s global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.HighlightsNovel offline perturbational method applied on functional magnetic resonance imaging (fMRI) data under the effect of lysergic acid diethylamide (LSD)Shift of brain’s global working point to more complex dynamics after LSD intakeConsistently longer recovery time after model perturbation under LSD influenceStrongest effects in resting state networks relevant for psychedelic experienceHigher response diversity across brain regions under LSD influence after an external in silico perturbation

scholarly journals A Systematic Review of Obesity and Binge Eating Associated Impairment of the Cognitive Inhibition System

2021 ◽  
Vol 8 ◽  
Author(s):  
Elodie Saruco ◽  
Burkhard Pleger
Keyword(s):  
Systematic Review ◽  
Eating Disorder ◽  
Binge Eating ◽  
Binge Eating Disorder ◽  
Neural Circuits ◽  
Brain Regions ◽  
Cognitive Inhibition ◽  
Significant Impairment ◽  
Disinhibited Eating ◽  
The Brain

Altered functioning of the inhibition system and the resulting higher impulsivity are known to play a major role in overeating. Considering the great impact of disinhibited eating behavior on obesity onset and maintenance, this systematic review of the literature aims at identifying to what extent the brain inhibitory networks are impaired in individuals with obesity. It also aims at examining whether the presence of binge eating disorder leads to similar although steeper neural deterioration. We identified 12 studies that specifically assessed impulsivity during neuroimaging. We found a significant alteration of neural circuits primarily involving the frontal and limbic regions. Functional activity results show BMI-dependent hypoactivity of frontal regions during cognitive inhibition and either increased or decreased patterns of activity in several other brain regions, according to their respective role in inhibition processes. The presence of binge eating disorder results in further aggravation of those neural alterations. Connectivity results mainly report strengthened connectivity patterns across frontal, parietal, and limbic networks. Neuroimaging studies suggest significant impairment of various neural circuits involved in inhibition processes in individuals with obesity. The elaboration of accurate therapeutic neurocognitive interventions, however, requires further investigations, for a deeper identification and understanding of obesity-related alterations of the inhibition brain system.

scholarly journals Automatic Detection of Synaptic Partners in a Whole-Brain Drosophila EM Dataset

2019 ◽  
Author(s):  
Julia Buhmann ◽  
Arlo Sheridan ◽  
Stephan Gerhard ◽  
Renate Krause ◽  
Tri Nguyen ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Brain Regions ◽  
High Accuracy ◽  
Automatic Method ◽  
Synaptic Connections ◽  
Whole Brain ◽  
Connectivity Graph ◽  
Automatic Retrieval ◽  
Strongly Connected ◽  
Automatic Methods

AbstractThe study of neural circuits requires the reconstruction of neurons and the identification of synaptic connections between them. To scale the reconstruction to the size of whole-brain datasets, semi-automatic methods are needed to solve those tasks. Here, we present an automatic method for synaptic partner identification in insect brains, which uses convolutional neural networks to identify post-synaptic sites and their pre-synaptic partners. The networks can be trained from human generated point annotations alone and require only simple post-processing to obtain final predictions. We used our method to extract 244 million putative synaptic partners in the fifty-teravoxel full adult fly brain (FAFB) electron microscopy (EM) dataset and evaluated its accuracy on 146,643 synapses from 702 neurons with a total cable length of 312 mm in four different brain regions. The predicted synaptic connections can be used together with a neuron segmentation to infer a connectivity graph with high accuracy: between 92% and 96% of edges linking connected neurons are correctly classified as weakly connected (less than five synapses) and strongly connected (at least five synapses). Our synaptic partner predictions for the FAFB dataset are publicly available, together with a query library allowing automatic retrieval of up- and downstream neurons.

scholarly journals Relative Brain Size and Its Relation with the Associative Pallium in Birds

2016 ◽  
Vol 87 (2) ◽  
pp. 69-77 ◽  
Author(s):  
Ferran Sayol ◽  
Louis Lefebvre ◽  
Daniel Sol
Keyword(s):  
Brain Size ◽  
Large Fraction ◽  
Biological Significance ◽  
Size Variation ◽  
Brain Structures ◽  
Brain Regions ◽  
Whole Brain ◽  
Small Areas ◽  
Mosaic Evolution ◽  
The Brain

Despite growing interest in the evolution of enlarged brains, the biological significance of brain size variation remains controversial. Much of the controversy is over the extent to which brain structures have evolved independently of each other (mosaic evolution) or in a coordinated way (concerted evolution). If larger brains have evolved by the increase of different brain regions in different species, it follows that comparisons of the whole brain might be biologically meaningless. Such an argument has been used to criticize comparative attempts to explain the existing variation in whole-brain size among species. Here, we show that pallium areas associated with domain-general cognition represent a large fraction of the entire brain, are disproportionally larger in large-brained birds and accurately predict variation in the whole brain when allometric effects are appropriately accounted for. While this does not question the importance of mosaic evolution, it suggests that examining specialized, small areas of the brain is not very helpful for understanding why some birds have evolved such large brains. Instead, the size of the whole brain reflects consistent variation in associative pallium areas and hence is functionally meaningful for comparative analyses.

scholarly journals Network analysis of whole-brain fMRI dynamics: A new framework based on dynamic communicability

2018 ◽  
Author(s):  
Matthieu Gilson ◽  
Nikos E. Kouvaris ◽  
Gustavo Deco ◽  
Jean-François Mangin ◽  
Cyril Poupon ◽  
...  
Keyword(s):  
Network Analysis ◽  
Network Theory ◽  
Random Network ◽  
Effective Connectivity ◽  
Structural Connectivity ◽  
Real Data ◽  
Brain Regions ◽  
Network Activity ◽  
Whole Brain ◽  
The Brain

AbstractNeuroimaging techniques such as MRI have been widely used to explore the associations between brain areas. Structural connectivity (SC) captures the anatomical pathways across the brain and functional connectivity (FC) measures the correlation between the activity of brain regions. These connectivity measures have been much studied using network theory in order to uncover the distributed organization of brain structures, in particular FC for task-specific brain communication. However, the application of network theory to study FC matrices is often “static” despite the dynamic nature of time series obtained from fMRI. The present study aims to overcome this limitation by introducing a network-oriented analysis applied to whole-brain effective connectivity (EC) useful to interpret the brain dynamics. Technically, we tune a multivariate Ornstein-Uhlenbeck (MOU) process to reproduce the statistics of the whole-brain resting-state fMRI signals, which provides estimates for MOU-EC as well as input properties (similar to local excitabilities). The network analysis is then based on the Green function (or network impulse response) that describes the interactions between nodes across time for the estimated dynamics. This model-based approach provides time-dependent graph-like descriptor, named communicability, that characterize the roles that either nodes or connections play in the propagation of activity within the network. They can be used at both global and local levels, and also enables the comparison of estimates from real data with surrogates (e.g. random network or ring lattice). In contrast to classical graph approaches to study SC or FC, our framework stresses the importance of taking the temporal aspect of fMRI signals into account. Our results show a merging of functional communities over time (in which input properties play a role), moving from segregated to global integration of the network activity. Our formalism sets a solid ground for the analysis and interpretation of fMRI data, including task-evoked activity.

scholarly journals Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits

2018 ◽  
Author(s):  
Jerzy O. Szablowski ◽  
Brian Lue ◽  
Audrey Lee-Gosselin ◽  
Dina Malounda ◽  
Mikhail G. Shapiro
Keyword(s):  
Neural Circuits ◽  
Brain Regions ◽  
Cell Type ◽  
Spatial Targeting ◽  
Temporal Specificity ◽  
Cell Type Specific ◽  
Orally Bioavailable ◽  
G Protein Coupled ◽  
The Brain ◽  
Spatial Cell

ABSTRACTNeurological and psychiatric diseases often involve the dysfunction of specific neural circuits in particular regions of the brain. Existing treatments, including drugs and implantable brain stimulators, aim to modulate the activity of these circuits, but are typically not cell type-specific, lack spatial targeting or require invasive procedures. Here, we introduce an approach to modulating neural circuits noninvasively with spatial, cell-type and temporal specificity. This approach, called acoustically targeted chemogenetics, or ATAC, uses transient ultrasonic opening of the blood brain barrier to transduce neurons at specific locations in the brain with virally-encoded engineered G-protein-coupled receptors, which subsequently respond to systemically administered bio-inert compounds to activate or inhibit the activity of these neurons. We demonstrate this concept in mice by using ATAC to noninvasively modify and subsequently activate or inhibit excitatory neurons within the hippocampus, showing that this enables pharmacological control of memory formation. This technology allows a brief, noninvasive procedure to make one or more specific brain regions capable of being selectively modulated using orally bioavailable compounds, thereby overcoming some of the key limitations of conventional brain therapies.

scholarly journals A null model of the mouse whole-neocortex micro-connectome

2019 ◽  
Author(s):  
Michael W Reimann ◽  
Michael Gevaert ◽  
Ying Shi ◽  
Huanxiang Lu ◽  
Henry Markram ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Null Model ◽  
Brain Regions ◽  
Whole Brain ◽  
Micro Scale ◽  
Connectivity Patterns ◽  
Experimental Findings ◽  
The Brain ◽  
Scale Data ◽  
Meso Scale

1AbstractConnectomics, the study of the structure of networks of synaptically connected neurons, is one of the most important frontiers of neuroscience. Great advances are being made on the level of macro- and meso-scale connectomics, that is the study of how and which populations of neurons are wired together by tracing axons of anatomically and genetically defined neurons throughout the brain. Similarly, the use of electron-microscopy and statistical connectome models has improved our understanding of micro-connectomics, that is the study of connectivity patterns between individual neurons. We have combined these two complementary views of connectomics to build a first draft statistical model of the neuron-to-neuron micro-connectome of a whole mouse neocortex. We combined available data on region-to-region connectivity and individual whole-brain axon reconstructions to model in addition to the meso-scale trends also the innervation of individual neurons by individual axons, within and across regions. This process revealed a novel targeting principle that allowed us to predict the innervation logic of individual axons from meso-scale data. The resulting micro-connectome of 10 million neurons and 88 billion synapses recreates biological trends of targeting on the macro-meso- and micro-scale, i.e. targeting of brain regions, domains and layers within a brain region down to individual neurons. This openly accessible connectome can serve as a powerful null model to compare experimental findings to and as a substrate for whole-brain simulations of detailed neural networks.

Learning, Neurogenesis, and Effects of Flavonoids on Learning

2021 ◽  
Vol 21 ◽  
Author(s):  
Asan Yalmaz Hasan Almulla ◽  
Rasim Mogulkoc ◽  
Abdulkerim Kasim Baltaci ◽  
Dervis Dasdelen
Keyword(s):  
Learning And Memory ◽  
Neural Circuits ◽  
Brain Regions ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Factors Affecting ◽  
Different Types ◽  
Mature Neurons ◽  
Dependent Learning ◽  
The Brain

: Learning and memory are two of our mind's most magical abilities. Different brain regions have roles in processing and storing different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis, which is a process in which new neurons are produced and then transformed into mature neurons and finally integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network; this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can particularly exert powerful actions in mammalian cognition and improve hippocampal-dependent learning and memory by positively affecting hippocampal neurogenesis.

scholarly journals Qualitative and Quantitative Analysis of Regional Cerebral Free Fatty Acids in Rats Using the Stable Isotope Labeling Liquid Chromatography–Mass Spectrometry Method

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5163
Author(s):  
Ting Hu ◽  
Quanfei Zhu ◽  
Yuning Hu ◽  
Ghulam Mustafa Kamal ◽  
Yuqi Feng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Liquid Chromatography ◽  
Olfactory Bulb ◽  
Free Fatty Acids ◽  
Brain Regions ◽  
Liquid Chromatography Mass Spectrometry ◽  
Whole Brain ◽  
The Relationship ◽  
The Brain

Free fatty acids serve as important bioactive molecules in the brain. They are involved in message transfer in the brain. There are many reports available in the literature regarding the role of cerebral fatty acids in message transfer; however, most of the studies are mainly focused on limited fatty acid species or only a few specific brain regions. To understand the relationship between cerebral functions and free fatty acids, it is necessary to investigate the distribution of the free fatty acids among different regions in the whole brain. In this study, free fatty acids were extracted from different brain regions and analyzed qualitatively and quantitatively using the stable isotopic labeling liquid chromatography–mass spectrometry approach. In total, 1008 potential free fatty acids were detected in the whole brain out of which 38 were found to be commonly present in all brain regions. Among different brain regions, the highest and the smallest amounts of potential free fatty acids were detected in the olfactory bulb and cerebellum, respectively. From a statistical point of view, 4-methyl-2-oxovaleric acid, cis-11, 14-eicosadienoic acid, tridecanoic acid, myristic acid, nonadecanoic acid, and arachidic acid were found to significantly vary among the four different brain regions (olfactory bulb, occipital lobe, hippocampus, and cerebellum). The variation in the composition of free fatty acids among different brain regions may be very important for investigating the relationship between free fatty acids and functions of cerebral regions.

scholarly journals Stress-induced microglial activation occurs through β-adrenergic receptor: noradrenaline as a key neurotransmitter in microglial activation

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shuei Sugama ◽  
Takato Takenouchi ◽  
Makoto Hashimoto ◽  
Hisayuki Ohata ◽  
Yasuhiro Takenaka ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Microglial Activation ◽  
Acute Stress ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Laser Scanning Microscopy ◽  
Double Knockout ◽  
Whole Brain ◽  
Β Blocker ◽  
The Brain

Abstract Background The involvement of microglia in neuroinflammatory responses has been extensively demonstrated. Recent animal studies have shown that exposure to either acute or chronic stress induces robust microglial activation in the brain. In the present study, we investigated the underlying mechanism of brain microglial activation by acute stress. Methods We first looked at the spatial distribution of the noradrenaline (NA)-synthesizing enzyme, DBH (dopamine β-hydroxylase), in comparison with NA receptors—β1, β2, and β3 adrenergic receptors (β1-AR, β2-AR, and β3-AR)—after which we examined the effects of the β-blocker propranolol and α-blockers prazosin and yohimbine on stress-induced microglial activation. Finally, we compared stress-induced microglial activation between wild-type (WT) mice and double-knockout (DKO) mice lacking β1-AR and β2-AR. Results The results demonstrated that (1) microglial activation occurred in most studied brain regions, including the hippocampus (HC), thalamus (TM), and hypothalamus (HT); (2) within these three brain regions, the NA-synthesizing enzyme DBH was densely stained in the neuronal fibers; (3) β1-AR and β2-AR, but not β3-AR, are detected in the whole brain, and β1-AR and β2-AR are co-localized with microglial cells, as observed by laser scanning microscopy; (4) β-blocker treatment inhibited microglial activation in terms of morphology and count through the whole brain; α-blockers did not show such effect; (5) unlike WT mice, DKO mice exhibited substantial inhibition of stress-induced microglial activation in the brain. Conclusions We demonstrate that neurons/microglia may interact with NA via β1-AR and β2-AR.

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