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Book ; Online: Current Views of Hypothalamic Contributions to the Control of Motivated Behaviors

Hahn, Joel D. / Fink, George / Kruk, Menno R. / Glenn Stanley, B.

2019

Keywords	Science: general issues ; Neurosciences ; Hypothalamus ; motivated behaviors ; motor control ; Innate behaviors
Size	1 electronic resource (140 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021230240
ISBN	9782889631995 ; 2889631990
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: A brain flatmap data visualization tool for mouse, rat, and human.

Hahn, Joel D / Duckworth, Chloe

The Journal of comparative neurology

2023 Volume 531, Issue 10, Page(s) 1008–1016

Abstract: Here we provide open-access brain data flatmap visualization and analysis tools for the mouse, rat, and human. The present work stems from a previous JCN Toolbox article that introduced a novel flatmap of the mouse brain and substantially enhanced ... ...

Abstract	Here we provide open-access brain data flatmap visualization and analysis tools for the mouse, rat, and human. The present work stems from a previous JCN Toolbox article that introduced a novel flatmap of the mouse brain and substantially enhanced flatmaps of the rat and human brain. These brain flatmap data visualization tools enable computer-generated graphical flatmap representation of tabulated user-entered data. For mouse and rat, they are designed to accommodate data resolved spatially up to the level of gray matter regions, supported by parcellation and nomenclature defined in current brain reference atlases. For human, Brodmann cerebral cortical parcellation is emphasized, and all other major brain divisions are represented. A comprehensive user guide is included along with several use examples. These brain data visualization tools enable the tabulation and automatic graphical flatmap representation of any type of mouse, rat, or human brain data that is spatially localized. The formalized presentation afforded by these graphical tools facilitates comparative analysis between data sets within or between the represented species.
MeSH term(s)	Humans ; Rats ; Mice ; Animals ; Data Visualization ; Brain ; Gray Matter ; Neuroimaging ; Cerebral Cortex
Language	English
Publishing date	2023-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.25478
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Article ; Online: Network architecture of intrinsic connectivity in a mammalian spinal cord (the central nervous system's caudal sector).

Swanson, Larry W / Hahn, Joel D / Sporns, Olaf

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 5, Page(s) e2320953121

Abstract: The vertebrate spinal cord (SP) is the long, thin extension of the brain forming the central nervous system's caudal sector. Functionally, the SP directly mediates motor and somatic sensory interactions with most parts of the body except the face, and it ...

Abstract	The vertebrate spinal cord (SP) is the long, thin extension of the brain forming the central nervous system's caudal sector. Functionally, the SP directly mediates motor and somatic sensory interactions with most parts of the body except the face, and it is the preferred model for analyzing relatively simple reflex behaviors. Here, we analyze the organization of axonal connections between the 50 gray matter regions forming the bilaterally symmetric rat SP. The assembled dataset suggests that there are about 385 of a possible 2,450 connections between the 50 regions for a connection density of 15.7%. Multiresolution consensus cluster analysis reveals a hierarchy of structure-function subsystems in this neural network, with 4 subsystems at the top level and 12 at the bottom-level. The top-level subsystems include a) a bilateral subsystem related most clearly to somatic and autonomic motor functions and centered in the ventral horn and intermediate zone; b) a bilateral subsystem associated with general somatosensory functions and centered in the base, neck, and head of the dorsal horn; and c) a pair of unilateral, bilaterally symmetric subsystems associated with nociceptive information processing and occupying the apex of the dorsal horn. The intrinsic SP network displayed no hubs, rich club, or small-world attributes, which are common measures of global functionality. Advantages and limitations of our methodology are discussed in some detail. The present work is part of a comprehensive project to assemble and analyze the neurome of a mammalian nervous system and its interactions with the body.
MeSH term(s)	Rats ; Animals ; Mammals ; Spinal Cord Dorsal Horn ; Gray Matter ; Axons ; Brain
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2320953121
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Article ; Online: Intrinsic circuitry of the rhombicbrain (central nervous system's intermediate sector) in a mammal.

Swanson, Larry W / Hahn, Joel D / Sporns, Olaf

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 52, Page(s) e2313997120

Abstract: The rhombicbrain (rhombencephalon or intermediate sector) is the vertebrate central nervous system part between the forebrain-midbrain (rostral sector) and spinal cord (caudal sector), and it has three main divisions: pons, cerebellum, and medulla. Using ...

Abstract	The rhombicbrain (rhombencephalon or intermediate sector) is the vertebrate central nervous system part between the forebrain-midbrain (rostral sector) and spinal cord (caudal sector), and it has three main divisions: pons, cerebellum, and medulla. Using a data-driven approach, here we examine intrinsic rhombicbrain (intrarhombicbrain) network architecture that in rat consists of 52,670 possible axonal connections between 230 gray matter regions (115 bilaterally symmetrical pairs). Our analysis indicates that only 8,089 (15.4%) of these connections exist. Multiresolution consensus cluster analysis yields a nested hierarchy model of rhombicbrain subsystems that at the top level are associated with 1) the cerebellum and vestibular nuclei, 2) orofacial-pharyngeal-visceral integration, and 3) auditory connections; the bottom level has 68 clusters, ranging in size from 2 to 11 regions. The model provides a basis for functional hypothesis development and interrogation. More granular network analyses performed on the intrinsic connectivity of individual and combined main rhombicbrain divisions (pons, cerebellum, medulla, pons + cerebellum, and pons + medulla) demonstrate the mutability of network architecture in response to the addition or subtraction of connections. Clear differences between the structure-function network architecture of the rhombicbrain and forebrain-midbrain are discussed, with a stark comparison provided by the subsystem and small-world organization of the cerebellar cortex and cerebral cortex. Future analysis of the connections within and between the forebrain-midbrain and rhombicbrain will provide a model of brain neural network architecture in a mammal.
MeSH term(s)	Rats ; Animals ; Cerebellum ; Pons ; Prosencephalon ; Central Nervous System ; Mammals
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2313997120
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Article ; Online: Structure-function subsystem model and computational lesions of the central nervous system's rostral sector (forebrain and midbrain).

Swanson, Larry W / Hahn, Joel D / Sporns, Olaf

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 45, Page(s) e2210931119

Abstract: The craniote central nervous system has been divided into rostral, intermediate, and caudal sectors, with the rostral sector containing the vertebrate forebrain and midbrain. Here, network science tools were used to create and analyze a rat hierarchical ... ...

Abstract	The craniote central nervous system has been divided into rostral, intermediate, and caudal sectors, with the rostral sector containing the vertebrate forebrain and midbrain. Here, network science tools were used to create and analyze a rat hierarchical structure-function subsystem model of intrarostral sector neural connectivity between gray matter regions. The hierarchy has 109 bottom-level subsystems and three upper-level subsystems corresponding to voluntary behavior control, cognition, and affect; instinctive survival behaviors and homeostasis; and oculomotor control. As in previous work, subsystems identified based on their coclassification as network communities are revealed as functionally related. We carried out focal perturbations of neural structural connectivity comprehensively by computationally lesioning each region of the network, and the resulting effects on the network's modular (subsystem) organization were systematically mapped and measured. The pattern of changes was found to be correlated with three structural attributes of the lesioned region: region centrality (degree, strength, and betweenness), region position in the hierarchy, and subsystem distribution of region neural outputs and inputs. As expected, greater region centrality results, on average, in stronger lesion impact and more distributed lesion effects. In addition, our analysis suggests that strongly functionally related regions, belonging to the same bottom-level subsystem, exhibit similar effects after lesioning. These similarities account for coherent patterns of disturbances that align with subsystem boundaries and propagate through the network. These systematic lesion effects and their similarity across functionally related regions are of potential interest for theoretical, experimental, and clinical studies.
MeSH term(s)	Animals ; Rats ; Prosencephalon/physiology ; Cerebral Cortex ; Mesencephalon
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2210931119
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: A qualitative solution with quantitative potential for the mouse hippocampal cortex flatmap problem.

Swanson, Larry W / Hahn, Joel D

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 6, Page(s) 3220–3231

Abstract: The hippocampal formation (HPF) is a focus of intense experimental investigation, particularly because of its roles in conscious memory consolidation, spatial navigation, emotion, and motivated behaviors. However, the HPF has a complex three-dimensional ... ...

Abstract	The hippocampal formation (HPF) is a focus of intense experimental investigation, particularly because of its roles in conscious memory consolidation, spatial navigation, emotion, and motivated behaviors. However, the HPF has a complex three-dimensional geometry resulting from extreme curvature of its layers, and this presents a challenge for investigators seeking to decipher hippocampal structure and function at cellular and molecular scales (neuronal circuitry, gene expression, and other properties). Previously, this problem was solved qualitatively for the rat by constructing a physical surface model of the HPF based on histological sections, and then deriving from the model a flatmap. Its usefulness is exemplified by previous studies that used it to display topological relationships between different components of intrahippocampal circuitry derived from experimental pathway-tracing experiments. Here the rat HPF flatmap was used as a starting point to construct an analogous flatmap for the mouse, where the great majority of experimental hippocampal research is currently performed. A detailed account of underlying knowledge and principles is provided, including for hippocampal terminology, and development from an embryonic nonfolded sheet into differentiated multiple adjacent cortical areas, giving rise to the adult shape. To demonstrate its utility, the mouse flatmap was used to display the results of pathway-tracing experiments showing the dentate gyrus mossy fiber projection, and its relationship to the intrahippocampal Purkinje cell protein 4 gene-expression pattern. Finally, requirements for constructing a computer graphics quantitative intrahippocampal flatmap, with accompanying intrahippocampal coordinate system, are presented; they should be applicable to all mammals, including human.
MeSH term(s)	Animals ; Hippocampus/anatomy & histology ; Hippocampus/physiology ; Humans ; Mice ; Neural Pathways/anatomy & histology ; Neural Pathways/physiology ; Parahippocampal Gyrus/anatomy & histology ; Parahippocampal Gyrus/physiology ; Rats
Language	English
Publishing date	2020-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1918907117
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Subsystem macroarchitecture of the intrinsic midbrain neural network and its tectal and tegmental subnetworks.

Swanson, Larry W / Hahn, Joel D / Sporns, Olaf

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 20

Abstract: The midbrain is the smallest of three primary vertebrate brain divisions. Here we use network science tools to reveal the global organizing principles of intramidbrain axonal circuitry before adding extrinsic connections with the remaining nervous system. ...

Abstract	The midbrain is the smallest of three primary vertebrate brain divisions. Here we use network science tools to reveal the global organizing principles of intramidbrain axonal circuitry before adding extrinsic connections with the remaining nervous system. Curating the experimental neuroanatomical literature yielded 17,248 connection reports for 8,742 possible connections between the 94 gray matter regions forming the right and left midbrain. Evidence for the existence of 1,676 connections suggests a 19.2% connection density for this network, similar to that for the intraforebrain network [L. W. Swanson
MeSH term(s)	Animals ; Mesencephalon/anatomy & histology ; Mesencephalon/physiology ; Nerve Net ; Rats ; Tectum Mesencephali/anatomy & histology ; Tegmentum Mesencephali/anatomy & histology
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2101869118
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Article ; Online: A folate inhibitor exploits metabolic differences in Pseudomonas aeruginosa for narrow-spectrum targeting.

Chain, Connor / Sheehan, Joseph P / Xu, Xincheng / Ghaffari, Soodabeh / Godbole, Aneesh / Kim, Hahn / Freundlich, Joel S / Rabinowitz, Joshua D / Gitai, Zemer

Nature microbiology

2024

Abstract: Pseudomonas aeruginosa is a leading cause of hospital-acquired infections for which the development of antibiotics is urgently needed. Unlike most enteric bacteria, P. aeruginosa lacks enzymes required to scavenge exogenous thymine. An appealing strategy ...

Abstract	Pseudomonas aeruginosa is a leading cause of hospital-acquired infections for which the development of antibiotics is urgently needed. Unlike most enteric bacteria, P. aeruginosa lacks enzymes required to scavenge exogenous thymine. An appealing strategy to selectively target P. aeruginosa is to disrupt thymidine synthesis while providing exogenous thymine. However, known antibiotics that perturb thymidine synthesis are largely inactive against P. aeruginosa.Here we characterize fluorofolin, a dihydrofolate reductase (DHFR) inhibitor derived from Irresistin-16, that exhibits significant activity against P. aeruginosa in culture and in a mouse thigh infection model. Fluorofolin is active against a wide range of clinical P. aeruginosa isolates resistant to known antibiotics. Metabolomics and in vitro assays using purified folA confirm that fluorofolin inhibits P. aeruginosa DHFR. Importantly, in the presence of thymine supplementation, fluorofolin activity is selective for P. aeruginosa. Resistance to fluorofolin can emerge through overexpression of the efflux pumps MexCD-OprJ and MexEF-OprN, but these mutants also decrease pathogenesis. Our findings demonstrate how understanding species-specific genetic differences can enable selective targeting of important pathogens while revealing trade-offs between resistance and pathogenesis.
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-024-01665-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Structure-function subsystem models of female and male forebrain networks integrating cognition, affect, behavior, and bodily functions.

Swanson, Larry W / Hahn, Joel D / Sporns, Olaf

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 49, Page(s) 31470–31481

Abstract: The forebrain is the first of three primary vertebrate brain subdivisions. Macrolevel network analysis in a mammal (rat) revealed that the 466 gray matter regions composing the right and left sides of the forebrain are interconnected by 35,738 axonal ... ...

Abstract	The forebrain is the first of three primary vertebrate brain subdivisions. Macrolevel network analysis in a mammal (rat) revealed that the 466 gray matter regions composing the right and left sides of the forebrain are interconnected by 35,738 axonal connections forming a large set of overlapping, hierarchically arranged subsystems. This hierarchy is bilaterally symmetrical and sexually dimorphic, and it was used to create a structure-function conceptual model of intraforebrain network organization. Two mirror image top-level subsystems are presumably the most fundamental ontogenetically and phylogenetically. They essentially form the right and left forebrain halves and are relatively weakly interconnected. Each top-level subsystem in turn has two second-level subsystems. A ventromedial subsystem includes the medial forebrain bundle, functionally coordinating instinctive survival behaviors with appropriate physiological responses and affect. This subsystem has 26/24 (female/male) lowest-level subsystems, all using a combination of glutamate and GABA as neurotransmitters. In contrast, a dorsolateral subsystem includes the lateral forebrain bundle, functionally mediating voluntary behavior and cognition. This subsystem has 20 lowest-level subsystems, and all but 4 use glutamate exclusively for their macroconnections; no forebrain subsystems are exclusively GABAergic. Bottom-up subsystem analysis is a powerful engine for generating testable hypotheses about mechanistic explanations of brain function, behavior, and mind based on underlying circuit organization. Targeted computational (virtual) lesioning of specific regions of interest associated with Alzheimer's disease, clinical depression, and other disorders may begin to clarify how the effects spread through the entire forebrain network model.
MeSH term(s)	Affect/physiology ; Alzheimer Disease/physiopathology ; Animals ; Behavior, Animal/physiology ; Cognition/physiology ; Depression/physiopathology ; Female ; Male ; Models, Neurological ; Nerve Net/physiology ; Prosencephalon/physiology ; Rats ; Taste/physiology
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2017733117
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Article ; Online: Macroscale connections of the mouse lateral preoptic area and anterior lateral hypothalamic area.

Hahn, Joel D / Gao, Lei / Boesen, Tyler / Gou, Lin / Hintiryan, Houri / Dong, Hong-Wei

The Journal of comparative neurology

2022 Volume 530, Issue 13, Page(s) 2254–2285

Abstract: The macroscale neuronal connections of the lateral preoptic area (LPO) and the caudally adjacent lateral hypothalamic area anterior region (LHAa) were investigated in mice by anterograde and retrograde axonal tracing. Both hypothalamic regions are highly ...

Abstract	The macroscale neuronal connections of the lateral preoptic area (LPO) and the caudally adjacent lateral hypothalamic area anterior region (LHAa) were investigated in mice by anterograde and retrograde axonal tracing. Both hypothalamic regions are highly and diversely connected, with connections to >200 gray matter regions spanning the forebrain, midbrain, and rhombicbrain. Intrahypothalamic connections predominate, followed by connections with the cerebral cortex and cerebral nuclei. A similar overall pattern of LPO and LHAa connections contrasts with substantial differences between their input and output connections. Strongest connections include outputs to the lateral habenula, medial septal and diagonal band nuclei, and inputs from rostral and caudal lateral septal nuclei; however, numerous additional robust connections were also observed. The results are discussed in relation to a current model for the mammalian forebrain network that associates LPO and LHAa with a range of functional roles, including reward prediction, innate survival behaviors (including integrated somatomotor and physiological control), and affect. The present data suggest a broad and intricate role for LPO and LHAa in behavioral control, similar in that regard to previously investigated LHA regions, contributing to the finely tuned sensory-motor integration that is necessary for behavioral guidance supporting survival and reproduction.
MeSH term(s)	Animals ; Cerebral Cortex ; Hypothalamic Area, Lateral ; Hypothalamus ; Mammals ; Mice ; Preoptic Area ; Septal Nuclei
Language	English
Publishing date	2022-05-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.25331
Database	MEDical Literature Analysis and Retrieval System OnLINE

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