The NeuARt II system: a viewing tool for neuroanatomical data based on published neuroanatomical atlases

BACKGROUND: Anatomical studies of neural circuitry describing the basic wiring diagram of the brain produce intrinsically spatial, highly complex data of great value to the neuroscience community. Published neuroanatomical atlases provide a spatial framework for these studies. We have built an informatics framework based on these atlases for the representation of neuroanatomical knowledge. This framework not only captures current methods of anatomical data acquisition and analysis, it allows these studies to be collated, compared and synthesized within a single system. RESULTS: We have developed an atlas-viewing application ('NeuARt II') in the Java language with unique functional properties. These include the ability to use copyrighted atlases as templates within which users may view, save and retrieve data-maps and annotate them with volumetric delineations. NeuARt II also permits users to view multiple levels on multiple atlases at once. Each data-map in this system is simply a stack of vector images with one image per atlas level, so any set of accurate drawings made onto a supported atlas (in vector graphics format) could be uploaded into NeuARt II. Presently the database is populated with a corpus of high-quality neuroanatomical data from the laboratory of Dr Larry Swanson (consisting 64 highly-detailed maps of PHAL tract-tracing experiments, made up of 1039 separate drawings that were published in 27 primary research publications over 17 years). Herein we take selective examples from these data to demonstrate the features of NeuArt II. Our informatics tool permits users to browse, query and compare these maps. The NeuARt II tool operates within a bioinformatics knowledge management platform (called 'NeuroScholar') either as a standalone or a plug-in application. CONCLUSION: Anatomical localization is fundamental to neuroscientific work and atlases provide an easily-understood framework that is widely used by neuroanatomists and non-neuroanatomists alike. NeuARt II, the neuroinformatics tool presented here, provides an accurate and powerful way of representing neuroanatomical data in the context of commonly-used brain atlases for visualization, comparison and analysis. Furthermore, it provides a framework that supports the delivery and manipulation of mapped data either as a standalone system or as a component in a larger knowledge management system

A Comparative Analysis Shows Morphofunctional Differences between the Rat and Mouse Melanin-Concentrating Hormone Systems

Sub-populations of neurons producing melanin-concentrating hormone (MCH) are characterized by distinct projection patterns, birthdates and CART/NK3 expression in rat. Evidence for such sub-populations has not been reported in other species. However, given that genetically engineered mouse lines are now commonly used as experimental models, a better characterization of the anatomy and morphofunctionnal organization of MCH system in this species is then necessary. Combining multiple immunohistochemistry experiments with in situ hybridization, tract tracing or BrdU injections, evidence supporting the hypothesis that rat and mouse MCH systems are not identical was obtained: sub-populations of MCH neurons also exist in mouse, but their relative abundance is different. Furthermore, divergences in the distribution of MCH axons were observed, in particular in the ventromedial hypothalamus. These differences suggest that rat and mouse MCH neurons are differentially involved in anatomical networks that control feeding and the sleep/wake cycle

Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans

The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social interactions and enhanced by vasopressin; however, the neural mechanisms mediating this effect in humans are unknown. Using functional magnetic resonance imaging (fMRI) and an implicit social recognition matching task, we employed a double-blinded procedure in which 20 healthy male volunteers self-administered 40 UI of vasopressin or placebo intranasally, 45 min before performing the matching task in the scanner. In a random-effects fMRI analysis, we show that vasopressin induces a regionally specific alteration in a key node of the theory of mind network, the left temporoparietal junction, identifying a neurobiological mechanism for prosocial neuropeptide effects in humans that suggests novel treatment strategies

Behavioral and Autonomic Responses to Acute Restraint Stress Are Segregated within the Lateral Septal Area of Rats

Background: The Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS. Methodology/Principal Findings: Male Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl2, 1 mM / 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM). Conclusions/Significance: Inhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperatur

The lateral septum mediates kinship behavior in the rat

Kinship behavior in rodents has been documented in the laboratory setting but the neural mechanisms that mediate kinship behavior are not known. Here, the authors show that the lateral septum has a key role in organizing mammalian kinship behavior

Hippocampal Volume Reduction in Congenital Central Hypoventilation Syndrome

Children with congenital central hypoventilation syndrome (CCHS), a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI) scans, with impaired responses in specific hippocampal regions, suggesting localized injury

Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio

Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways.

Methamphetamine (METH) addiction is a major public health problem in some countries. There is evidence to suggest that METH use is associated with increased risk of developing cardiovascular problems. Here, we investigated the effects of chronic METH administration and withdrawal on the activation of the brain stress system and cardiac sympathetic pathways. Mice were treated with METH (2 mg/kg, i.p.) for 10 days and left to spontaneous withdraw for 7 days. The number of corticotrophin-releasing factor (CRF), c-Fos, and CRF/c-Fos neurons was measured by immunohistochemistry in the paraventricular nucleus of the hypothalamus (PVN) and the oval region of the bed nucleus of stria terminalis (ovBNST), two regions associated with cardiac sympathetic control. In parallel, levels of catechol-o-methyl-transferase (COMT), tyrosine hydroxylase (TH), and heat shock protein 27 (Hsp27) were measured in the heart. In the brain, chronic-METH treatment enhanced the number of c-Fos neurons and the CRF neurons with c-Fos signal (CRF+/c-Fos+) in PVN and ovBNST. METH withdrawal increased the number of CRF+neurons. In the heart, METH administration induced an increase in soluble (S)-COMT and membrane-bound (MB)-COMT without changes in phospho (p)-TH, Hsp27, or pHsp27. Similarly, METH withdrawal increased the expression of S- and MB-COMT. In contrast to chronic treatment, METH withdrawal enhanced levels of (p)TH and (p)Hsp27 in the heart. Overall, our results demonstrate that chronic METH administration and withdrawal activate the brain CRF systems associated with the heart sympathetic control and point towards a METH withdrawal induced activation of sympathetic pathways in the heart. Our findings provide further insight in the mechanism underlining the cardiovascular risk associated with METH use and proposes targets for its treatment

Hippocampal pyramidal cells: the reemergence of cortical lamination

The increasing resolution of tract-tracing studies has led to the definition of segments along the transverse axis of the hippocampal pyramidal cell layer, which may represent functionally defined elements. This review will summarize evidence for a morphological and functional differentiation of pyramidal cells along the radial (deep to superficial) axis of the cell layer. In many species, deep and superficial sublayers can be identified histologically throughout large parts of the septotemporal extent of the hippocampus. Neurons in these sublayers are generated during different periods of development. During development, deep and superficial cells express genes (Sox5, SatB2) that also specify the phenotypes of superficial and deep cells in the neocortex. Deep and superficial cells differ neurochemically (e.g. calbindin and zinc) and in their adult gene expression patterns. These markers also distinguish sublayers in the septal hippocampus, where they are not readily apparent histologically in rat or mouse. Deep and superficial pyramidal cells differ in septal, striatal, and neocortical efferent connections. Distributions of deep and superficial pyramidal cell dendrites and studies in reeler or sparsely GFP-expressing mice indicate that this also applies to afferent pathways. Histological, neurochemical, and connective differences between deep and superficial neurons may correlate with (patho-) physiological phenomena specific to pyramidal cells at different radial locations. We feel that an appreciation of radial subdivisions in the pyramidal cell layer reminiscent of lamination in other cortical areas may be critical in the interpretation of studies of hippocampal anatomy and function