scholarly journals Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

2019 ◽  
Vol 116 (15) ◽  
pp. 7503-7512 ◽  
Author(s):  
Liching Lo ◽  
Shenqin Yao ◽  
Dong-Wook Kim ◽  
Ali Cetin ◽  
Julie Harris ◽  
...  
Keyword(s):  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Feed Forward ◽  
Motor Processing ◽  
Central Processing ◽  
Indirect Feedback ◽  
High Level ◽  
High Degree ◽  
The Brain

Type 1 estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvlEsr1) play a causal role in the control of social behaviors, including aggression. Here we use six different viral-genetic tracing methods to systematically map the connectional architecture of VMHvlEsr1 neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (∼90%) of bidirectionality, including both direct as well as indirect feedback. Unbiased collateralization mapping experiments indicate that VMHvlEsr1 neurons project to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization targets. Nevertheless, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired,” hierarchical feed-forward circuits used in certain types of artificial intelligence networks.

scholarly journals Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

2018 ◽  
Author(s):  
Liching Lo ◽  
Dong-Wook Kim ◽  
Shenqin Yao ◽  
Ali Cetin ◽  
Julie Harris ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Social Behaviors ◽  
Ventromedial Hypothalamus ◽  
Cellular Heterogeneity ◽  
Feed Forward ◽  
Motor Processing ◽  
Central Processing ◽  
Processing Stream ◽  
Hypothalamic Nuclei ◽  
Processing Circuit

ABSTRACTType 1 Estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvlEsr1) play a causal role in the control of social behaviors including aggression. Here we use six different viral-genetic tracing methods to map the connectional architecture of VMHvlEsr1 neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (~90%) of recurrence. Unlike GABAergic populations in other hypothalamic nuclei controlling feeding and parenting behavior, VMHvlEsr1 glutamatergic neurons collateralize to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization patterns. Surprisingly, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired” feed-forward circuits used in certain types of artificial intelligence networks.SIGNIFICANCEHow the cellular heterogeneity of brain nuclei maps onto circuit connectivity, the relationship of this anatomical mapping to behavioral function, and whether there are general principles underlying this relationship, remains poorly understood. Here we systematically map the connectivity of estrogen receptor-1-expressing neurons in the ventromedial hypothalamus (VMHvlEsr1), which control aggression and other social behaviors. We find that a relatively sparse, anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. Further, the VMHvl contains at least two subpopulations of Esr1+ neurons with different cell body characteristics and locations, with distinct patterns of collateralization to downstream targets. Nevertheless, these projection-defined subpopulations receive similar inputs. This input-output organization appears distinct from those described in other hypothalamic nuclei.

Mechanism of the induction of brain c-Fos-positive neurons by lipid absorption

2007 ◽  
Vol 292 (1) ◽  
pp. R268-R273 ◽  
Author(s):  
Chun-Min Lo ◽  
Liyun Ma ◽  
Dian Ming Zhang ◽  
Rachel Lee ◽  
Abby Qin ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Lipid Absorption ◽  
Neuronal Activation ◽  
Positive Neuron ◽  
The Central Nervous System ◽  
Chylomicron Formation ◽  
The Brain

Many gastrointestinal meal-related signals are transmitted to the central nervous system via the vagus nerve and thereby control changes in meal size. The c-Fos-positive neuron has been used as a marker of neuronal activation after lipid meals to examine the contribution of a selective macronutrient on brain neurocircuit activity. In rats fed Intralipid, the c-Fos-positive neurons were highly stimulated in the nucleus of the solitary tract (NTS) and in the hypothalamus, including the paraventricular nucleus (PVN), arcuate nucleus of the hypothalamus (ARC), and ventromedial hypothalamus at 4 h lipid feeding. However, c-Fos-like immunoreactivity was markedly attenuated in these brain regions when chylomicron formation/secretion was blocked by Pluronic L-81. After lymph was diverted from the lymph cannulated animals, the rats had a lower number of c-Fos-positive cells in the NTS and ARC. In contrast, the rats had higher c-Fos-positive neurons in PVN. The present study also revealed that c-Fos-positive neurons induced by feeding of Intalipid were abolished by CCK type 1 receptor antagonist, Lorglumide. We conclude that the formation and/or secretion of chylomicron are critical steps for initiating neuronal activation in the brain.

scholarly journals An architectonic type principle in the development of laminar patterns of cortico-cortical connections

2021 ◽  
Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag
Keyword(s):  
Structural Connectivity ◽  
Macaque Monkey ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Cortical Connections ◽  
Cortical Projections ◽  
Structural Connections ◽  
High Degree ◽  
The Brain

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.

scholarly journals Neural Correlates of Group Bias During Natural Viewing

2018 ◽  
Vol 29 (8) ◽  
pp. 3380-3389
Author(s):  
Timothy J Andrews ◽  
Ryan K Smith ◽  
Richard L Hoggart ◽  
Philip I N Ulrich ◽  
Andre D Gouws
Keyword(s):  
Time Course ◽  
Social Groups ◽  
Sensory Information ◽  
Brain Regions ◽  
Group Differences ◽  
Neural Basis ◽  
Brain Responses ◽  
The World ◽  
High Level ◽  
The Brain

Abstract Individuals from different social groups interpret the world in different ways. This study explores the neural basis of these group differences using a paradigm that simulates natural viewing conditions. Our aim was to determine if group differences could be found in sensory regions involved in the perception of the world or were evident in higher-level regions that are important for the interpretation of sensory information. We measured brain responses from 2 groups of football supporters, while they watched a video of matches between their teams. The time-course of response was then compared between individuals supporting the same (within-group) or the different (between-group) team. We found high intersubject correlations in low-level and high-level regions of the visual brain. However, these regions of the brain did not show any group differences. Regions that showed higher correlations for individuals from the same group were found in a network of frontal and subcortical brain regions. The interplay between these regions suggests a range of cognitive processes from motor control to social cognition and reward are important in the establishment of social groups. These results suggest that group differences are primarily reflected in regions involved in the evaluation and interpretation of the sensory input.

Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1α to the brain

1998 ◽  
Vol 275 (2) ◽  
pp. E207-E212 ◽  
Author(s):  
Lawrence M. Maness ◽  
Abba J. Kastin ◽  
William A. Banks
Keyword(s):  
Brain Regions ◽  
Intravenous Injections ◽  
The Central Nervous System ◽  
Major Route ◽  
Grain Distribution ◽  
Interleukin 1Α ◽  
High Degree ◽  
The Brain ◽  
Silver Grains

Diffusion from brain regions lacking a blood-brain barrier (BBB) and saturable transport across capillaries are possible pathways for the entry of blood-borne interleukin-1α into the central nervous system (CNS). To assess the involvement of these putative routes, mice received intravenous injections of radioiodinated interleukin-1α, and their brains were subjected to emulsion autoradiography. The resulting patterns of silver grain distribution showed that diffusion of interleukin-1α from the choroid plexus and the subfornical organ was greatly restricted. These restrictive properties were quantified by the determination of D1/2 values, the distances needed for the concentration of silver grains to decrease by one-half. Within several brain regions, a subset of the microvasculature indicated transport of interleukin-1α across the BBB. Individual microvessels showed different patterns of transport ranging from robust to absent. The high degree of containment of blood-borne interleukin-1α within the regions lacking a BBB indicates that these sites cannot account for total delivery of the cytokine into the brain and suggests instead that the microvascular network may serve as the major route of entry into the CNS.

scholarly journals An architectonic type principle in the development of laminar patterns of cortico-cortical connections

2019 ◽  
Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag
Keyword(s):  
Structural Connectivity ◽  
Macaque Monkey ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Cortical Connections ◽  
Cortical Projections ◽  
Structural Connections ◽  
High Degree ◽  
The Brain

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the amount of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.

scholarly journals Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain

2018 ◽  
Vol 29 (9) ◽  
pp. 3828-3835 ◽  
Author(s):  
Qilong Xin ◽  
Laura Ortiz-Terán ◽  
Ibai Diez ◽  
David L Perez ◽  
Julia Ginsburg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Connectivity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Genetic Sequence ◽  
Cortical Areas ◽  
Cortical Regions ◽  
High Degree ◽  
The Brain

Abstract Individual differences in humans are driven by unique brain structural and functional profiles, presumably mediated in part through differential cortical gene expression. However, the relationships between cortical gene expression profiles and individual differences in large-scale neural network organization remain poorly understood. In this study, we aimed to investigate whether the magnitude of sequence alterations in regional cortical genes mapped onto brain areas with high degree of functional connectivity variability across individuals. First, human genetic expression data from the Allen Brain Atlas was used to identify protein-coding genes associated with cortical areas, which delineated the regional genetic signature of specific cortical areas based on sequence alteration profiles. Thereafter, we identified brain regions that manifested high degrees of individual variability by using test-retest functional connectivity magnetic resonance imaging and graph-theory analyses in healthy subjects. We found that rates of genetic sequence alterations shared a distinct spatial topography with cortical regions exhibiting individualized (highly-variable) connectivity profiles. Interestingly, gene expression profiles of brain regions with highly individualized connectivity patterns and elevated number of sequence alterations are devoted to neuropeptide-signaling-pathways and chemical-synaptic-transmission. Our findings support that genetic sequence alterations may underlie important aspects of brain connectome individualities in humans. Significance Statement: The neurobiological underpinnings of our individuality as humans are still an unsolved question. Although the notion that genetic variation drives an individual’s brain organization has been previously postulated, specific links between neural connectivity and gene expression profiles have remained elusive. In this study, we identified the magnitude of population-based sequence alterations in discrete cortical regions and compared them to the brain topological distribution of functional connectivity variability across an independent human sample. We discovered that brain regions with high degree of connectional individuality are defined by increased rates of genetic sequence alterations; these findings specifically implicated genes involved in neuropeptide-signaling pathways and chemical-synaptic transmission. These observations support that genetic sequence alterations may underlie important aspects of the emergence of the brain individuality across humans.

scholarly journals Consequences of recurrent hypoglycaemia on brain function in diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Rory J. McCrimmon
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species Generation ◽  
Short Review ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Dark Side ◽  
Glycaemic Variability ◽  
Increased Risk ◽  
The Brain ◽  
Recurrent Hypoglycaemia

AbstractThe discovery of insulin and its subsequent mass manufacture transformed the lives of people with type 1 and 2 diabetes. Insulin, however, was a drug with a ‘dark side’. It brought with it the risk of iatrogenic hypoglycaemia. In this short review, the cellular consequences of recurrent hypoglycaemia, with a particular focus on the brain, are discussed. Using the ventromedial hypothalamus as an exemplar, this review highlights how recurrent hypoglycaemia has an impact on the specialised cells in the brain that are critical to the regulation of glucose homeostasis and the counterregulatory response to hypoglycaemia. In these cells, recurrent hypoglycaemia initiates a series of adaptations that ensure that they are more resilient to subsequent hypoglycaemia, but this leads to impaired hypoglycaemia awareness and a paradoxical increased risk of severe hypoglycaemia. This review also highlights how hypoglycaemia, as an oxidative stressor, may also exacerbate chronic hyperglycaemia-induced increases in oxidative stress and inflammation, leading to damage to vulnerable brain regions (and other end organs) and accelerating cognitive decline. Pre-clinical research indicates that glucose recovery following hypoglycaemia is considered a period where reactive oxygen species generation and oxidative stress are pronounced and can exacerbate the longer-term consequence of chronic hypoglycaemia. It is proposed that prior glycaemic control, hypoglycaemia and the degree of rebound hyperglycaemia interact synergistically to accelerate oxidative stress and inflammation, which may explain why increased glycaemic variability is now increasingly considered a risk factor for the complications of diabetes. Graphical abstract

scholarly journals Herpes Simplex Virus Type 1 in the Brain, Apolipoprotein E Genotype and Alzheimer’s Disease

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Uwe Beffert ◽  
Philippe Bertrand ◽  
Danielle Champagne ◽  
Serge Gauthier ◽  
Judes Poirier
Keyword(s):  
Risk Factor ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Brain Regions ◽  
Ε4 Allele ◽  
Simplex Virus ◽  
The Brain ◽  
Hsv 1

The ε4 allele of apolipoprotein E (apoE) is an important risk factor for Alzheimer's disease (AD), however, it is not required nor sufficient to cause the disease on its own. Herpes viruses cause acute and chronic diseases of the central nervous system and have been implicated in AD. Using a sensitive polymerase chain reaction method, latent herpes simplex virus type 1 (HSV-1) has been detected from five different brain regions (hippocampus, frontal cortex, occipital cortex, cerebellum and striatum) of neuropathologically confirmed AD and control tissue. HSV-1 positivity was then correlated with AD, presence of the virus in specific brain regions, and apoE genotype. The results confirm that the ε4 allele of apoE is a risk factor for AD, while HSV-1 alone is not. This held true for all five brain regions examined. Furthermore, no synergy between the two factors could be found when any one of the brain regions was examined individually or when the data were pooled. These findings emphasize that the ε4 allele of apoE is a risk factor for AD and that HSV-1, either alone or in combination with apoE, does not represent an increased risk for AD. Furthermore, no particular brain region seems to be more infected with HSV-1 than another, even in those regions most affected in AD.

scholarly journals The Altered Anatomical Distribution of ACE2 in the Brain With Alzheimer’s Disease Pathology

2021 ◽  
Vol 9 ◽  
Author(s):  
Huan Cui ◽  
Si Su ◽  
Yan Cao ◽  
Chao Ma ◽  
Wenying Qiu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Cortex ◽  
Brain Regions ◽  
Basal Nucleus ◽  
Angiotensin Converting Enzyme 2 ◽  
The Central Nervous System ◽  
High Level ◽  
The Relationship ◽  
The Brain

The whole world is suffering from the coronavirus disease 2019 (COVID-19) pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through angiotensin-converting enzyme 2 (ACE2). Neurological manifestations in COVID-19 patients suggested the invasion of SARS-CoV-2 into the central nervous system. The present study mapped the expression level of ACE2 in 12 brain regions through immunohistochemistry and detected ACE2 in endothelial cells and non-vascular cells. The comparison among brain regions found that pons, visual cortex, and amygdala presented a relatively high level of ACE2. In addition, this study demonstrates that the protein level of ACE2 was downregulated in the basal nucleus, hippocampus and entorhinal cortex, middle frontal gyrus, visual cortex, and amygdala of the brain with Alzheimer’s disease (AD) pathology. Collectively, our results suggested that ACE2 was expressed discriminatorily at different human brain regions, which was downregulated in the brain with AD pathology. This may contribute to a comprehensive understanding of the neurological symptoms caused by SARS-CoV-2 and provide clues for further research on the relationship between COVID-19 and AD.

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