Prefrontal projections to the bed nuclei of the stria terminalis modulate the specificity of aversive memories.

Generalizing aversive memories helps organisms avoid danger, whereas discriminating between dissimilar situations promotes opportunistic behaviors. We identified a novel pathway that controls the contextual specificity of memory consolidation of inhibitory avoidance learning. Optogenetic inhibition of the rostral medial prefrontal cortex (mPFC)-to-anteroventral bed nuclei of the stria terminalis (avBST) pathway after a single footshock exacerbated stress hormonal output, and 2 d later promoted generalization to a novel context.

A Prefrontal→Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response.

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes.

Activity in a prefrontal-periaqueductal gray circuit overcomes behavioral and endocrine features of the passive coping stress response.

The question of how the brain links behavioral and biological features of defensive responses has remained elusive. The importance of this problem is underscored by the observation that behavioral passivity in stress coping is associated with elevations in glucocorticoid hormones, and each may carry risks for susceptibility to a host of stress-related diseases. Past work implicates the medial prefrontal cortex (mPFC) in the top-down regulation of stress-related behaviors; however, it is unknown whether such changes have the capacity to buffer against the longer-lasting biological consequences associated with aversive experiences.

Comparison of murine behavioural and physiological responses after forced exercise by electrical shock versus manual prodding.

New Findings: What is the central question of this study? Forced treadmill exercise using electrical shock is the most common technique in rodent exercise studies. Here, we examined how the use of electrical shock during forced treadmill exercise affects behavioural and physiological responses in comparison to a novel non-electrical shock technique. What is the main finding and its importance? In comparison to mice that underwent traditional treadmill running induced by electrical shock, mice that underwent forced running using a novel technique involving gentle prodding to induce running showed: (i) higher locomotor activity; (ii) less anxiety-like behaviour; and (iii) altered exercise-induced muscle pain immediately after exercise.

Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits.

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention.

Evidence for Similar Prefrontal Structural and Functional Alterations in Male and Female Rats Following Chronic Stress or Glucocorticoid Exposure.

Previous work of ours and others has documented regressive changes in neuronal architecture and function in the medial prefrontal cortex (mPFC) of male rats following chronic stress. As recent focus has shifted toward understanding whether chronic stress effects on mPFC are sexually dimorphic, here we undertake a comprehensive analysis to address this issue. First, we show that chronic variable stress (14-day daily exposure to different challenges) resulted in a comparable degree of adrenocortical hyperactivity, working memory impairment, and dendritic spine loss in mPFC pyramidal neurons in both sexes.

Prefrontal-Bed Nucleus Circuit Modulation of a Passive Coping Response Set.

One of the challenges facing neuroscience entails localization of circuits and mechanisms accounting for how multiple features of stress responses are organized to promote survival during adverse experiences. The rodent medial prefrontal cortex (mPFC) is generally regarded as a key site for cognitive and affective information processing, and the anteroventral bed nuclei of the stria terminalis (avBST) integrates homeostatic information from a variety of sources, including the mPFC. Thus, we proposed that the mPFC is capable of generating multiple features (endocrine, behavioral) of adaptive responses via its influence over the avBST.

A Basal Forebrain Site Coordinates the Modulation of Endocrine and Behavioral Stress Responses via Divergent Neural Pathways.

Unlabelled: The bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH). Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure. Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress.

Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex.

The stress-responsive hypothalamo-pituitary-adrenal (HPA) axis plays a central role in promoting adaptations acutely, whereas adverse effects on physiology and behavior following chronic challenges may result from overactivity of this system. Elevations in glucocorticoids, the end-products of HPA activation, play roles in adaptive and maladaptive processes by targeting cognate receptors throughout neurons in limbic cortical networks to alter synaptic functioning. Because previous work has shown that chronic stress leads to functionally relevant regressive alterations in dendritic spine shape and number in pyramidal neurons in the medial prefrontal cortex (mPFC), this study examines the capacity of sustained increases in circulating corticosterone (B) alone to alter dendritic spine morphology and density in this region.

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation.

Unlabelled: The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC.

Adrenocortical status predicts the degree of age-related deficits in prefrontal structural plasticity and working memory.

Cognitive decline in aging is marked by considerable variability, with some individuals experiencing significant impairments and others retaining intact functioning. Whereas previous studies have linked elevated hypothalamo-pituitary-adrenal (HPA) axis activity with impaired hippocampal function during aging, the idea has languished regarding whether such differences may underlie the deterioration of other cognitive functions. Here we investigate whether endogenous differences in HPA activity are predictive of age-related impairments in prefrontal structural and behavioral plasticity.

Chronic stress-induced alterations of dendritic spine subtypes predict functional decrements in an hypothalamo-pituitary-adrenal-inhibitory prefrontal circuit.

Activation of the hypothalamo-pituitary-adrenal (HPA) axis plays a vital role in promoting adaptation during acute stress, but adverse effects of chronic stress may result from overactivity of this system. Recent evidence highlights a subdivision of GABAergic neurons within anterior bed nuclei of the stria terminalis (aBST) that integrates and relays inhibitory influences to HPA-effector neurons in paraventricular hypothalamus during acute stress, notably from medial prefrontal [prelimbic (PL)] and hippocampal [ventral subiculum (vSUB)] cortical fields. Here we localize the site and candidate mechanism of neuroplasticity within upstream regions of this inhibitory network after chronic variable stress (CVS).

Low level bacterial endotoxin activates two distinct signaling pathways in human peripheral blood mononuclear cells.

Background: Bacterial endotoxin, long recognized as a potent pro-inflammatory mediator in acute infectious processes, has more recently been identified as a risk factor for atherosclerosis and other cardiovascular diseases. When endotoxin enters the bloodstream, one of the first cells activated is the circulating monocyte, which exhibits a wide range of pro-inflammatory responses.

Methods: We studied the effect of low doses of E.

Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding.

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots.

Surfactant protein D is expressed and modulates inflammatory responses in human coronary artery smooth muscle cells.

Surfactant protein D (SP-D) is a constituent of the innate immune system that plays a role in the host defense against lung pathogens and in modulating inflammatory responses. While SP-D has been detected in extrapulmonary tissues, little is known about its expression and function in the vasculature. Immunostaining of human coronary artery tissue sections demonstrated immunoreactive SP-D protein in smooth muscle cells (SMCs) and endothelial cells.