Regulation of feline aggression by the bed nucleus of stria terminalis

The purpose of this experiment was to study the possible modulatory role of the bed nucleus of stria terminalis (BNST) in the regulation of affective defense and quiet biting attack reactions in the cat. The experimental paradigm employed concurrent electrical stimulation of the hypothalamic attack sites and of the BNST. The results of the present study demonstrate that concurrent electrical stimulation of the BNST can differentially modulate the two different forms of aggressive behavior by facilitating affective defense and by suppressing quiet biting attack.     

The bed nucleus of the stria terminalis modulates baroreflex in rats

In the present study, we report the effect of bed nucleus of stria terminalis (bed nucleus) ablation caused by bilateral microinjections of the nonselective synapse blocker CoCl2 on the baroreflex response in rats. Reversible ablation of the bed nucleus by bilateral microinjection of CoCl2 did not affect baseline blood pressure or heart rate, suggesting no tonic influence of bed nucleus on the cardiovascular system. Pretreatment with CoCl2 did not affect the tachycardic response to blood pressure decreases caused by intravenous infusion of sodium nitroprusside, but enhanced bradycardic responses evoked by blood pressure increases caused by intravenous infusion of phenylephrine. Present data suggest that synapses within the bed nucleus have a tonic inhibitory influence on the baroreflex parasympathetic component.     

Rat central amygdaloid nucleus projections to the bed nucleus of the stria terminalis.

The projections from the central amygdaloid nucleus (Ce) to different subdivisions of the bed nucleus of the stria terminalis (BNST) were investigated using retrograde transport of fluorescent dyes. Iontophoretic injections of either Fast Blue (FB) or bisbenzimide (BB) were applied to the anterior medial, posterior medial, anterior lateral and posterior lateral parts of the bed nucleus of the stria terminalis. The anterior medial BNST receives projections from caudal part of medial Ce (CeM). The posterior medial BNST receives projections specifically from the intermediate subdivision of Ce, though in some cases projections from the ventral subdivision (CeV) of Ce were seen. The anterior lateral BNST receives projections primarily from the caudal lateral Ce (CeL) as well as middle and caudal part of CeM. The posterior lateral BNST receives projection from rostral CeL as well as the CeV and lateral capsular Ce. In general, the results indicate that the major subdivisions of the BNST receive projections from Ce subdivisions having similar connections with diencephalic or brainstem cell groups. Additional evidence is presented suggesting that Ce-BNST projections are part of an extensive system of intrinsic connections linking similar groups of neurons in both the Ce and BNST as well as within Ce.     

Single-unit activity in the bed nucleus of the stria terminalis during fever

Arginine vasopressin, released from nerve terminals in the septal region, probably exerts endogenous antipyretic activity. A major source of vasopressin to this area is the bed nucleus of the stria terminalis (BST). In order to characterize electrophysiologically the BST-septal pathway and its potential role in the control of fever, single-unit, extracellular recordings were made from neurons in the BST of anesthetized rats. Afferent and efferent connections were identified by electrical stimulation of the medial amygdaloid nucleus and the ventral septal area (VSA). BST neurons received both inhibitory and excitatory synaptic input from the amygdala and VSA. Efferents to the VSA were identified by stimulus-evoked antidromic spike invasion. Some BST neurons were responsive to peripheral skin temperature (thermoresponsive). The activity of putative vasopressin neurons was studied during prostaglandin E1-induced fever. Although a majority of BST units was unaffected by fever, a proportion of the cells examined increased their firing rates in accordance with reported release of vasopressin in the VSA during fever.     

Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis

Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with [3H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to [3H]thymidine on E13-E14, E14-E15,... E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24-hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial "core" area just ventral to the fornix. For morphogenesis, pregnant females were given a single injection of [3H]thymidine during gestation, and their embryos were removed either 2 hours later (short survival) or in successive 24-hour periods (sequential survival). The embryonic brains were examined to locate areas of intensely labeled cells in the putative neuroepithelium of the strial bed nucleus, to trace migratory waves of young neurons, and to establish their final settling locations. Two different neuroepithelial sources produce neurons for the strial bed nucleus. The anterior strial bed nucleus is generated by a neuroepithelial zone at the base of the inferior horn of the lateral ventricle from the anterior commissural decussation area forward to the primordium of the nucleus accumbens.(ABSTRACT TRUNCATED AT 400 WORDS)     

Kindling of motor seizures from the bed nucleus of the stria terminalis.

Intermittent application of localized electrical stimulation to certain regions of the brain results in the development of generalized seizures (kindling effect); of all those regions the limbic system, and particularly the amygdala, is highly susceptible to this phenomenon. The kindling rate for different regions of the limbic system seems to be related to the extent of their anatomic connections with the amygdala. The present report deals with the kindling susceptibility of the bed nucleus of the stria terminalis (BST), a structure which has substantial direct connections with the amygdala and which has never been tested for this purpose. The BST was found to be among the structures having the highest susceptibility to kindling, just after the amygdala. Kindling of the BST was very similar to that in the amygdala but it did not result from an indirect activation of this last structure because we demonstrated that bilateral amygdalectomy did not prevent its development nor modify its expression. Several fiber tracts such as the stria terminalis and the anterior commissure surround or traverse the BST. We confirmed that motor seizures developed more rapidly when these fibers, rather than either the BST or the amygdala itself, were stimulated.     

Cardiovascular responses to electrical stimulation of the bed nucleus of the stria terminalis

To determine whether the influence of the bed nucleus of the stria terminalis (BST) on cardiovascular function can be localized to specific cytoarchitectural areas within the BST, urethane (1.3 g/kg)-anesthetized male Sprague-Dawley rats were probed for cardiovascular reactive sites. Electrical stimuli (50 μa, 50 Hz, and a 0.5 ms pulse duration), delivered through stereotaxically placed glass semimicroelectrodes, were localized to the BST. Sham-stimulated animals served as controls. Stimulation sites were correlated with cytoarchitecturally distinct areas within the BST, and changes in mean arterial pressure (MAP) were subjected to statistical analysis. Systematically probing the BST for cardiovascular reactive sites showed a correlation between evoked responses and distinct cytoarchitectural areas. Stimulation of the me dial BST produced increases in MAP; stimulation of the lateral aspect of the BST produced decreases in MAP. Both pressor and depressor responses were evoked from the area ventral to the anterior commissure. Pressor responses were elicited from the area immediatley ventral to the anterior commissure, and depressor responses followed stimulation of an area more ventral. All subnuclei showed corroborating cardiovascular responses to 20–30 n1 microinjection of sodium glutamate. Taken together, these data provide substantial evidence to indicate that the BST, particularly at more rostral areas, consists of a medial pressor area, a lateral depressor area, and a ventral area with both pressor and depressor zone. © 1995 Wiley-Liss, Inc.     

Neuroanatomical characterization of endogenous opioids in the bed nucleus of the stria terminalis

Numerous neuroanatomical data indicate that the bed nucleus of the stria terminalis (BST) provides an interface between cortical and amygdaloid neurons, and effector neurons modulating motor, autonomic and neuroendocrine responses. Distinct divisions of the BST may be involved in stress response, homeostatic regulation, nociception, and motivated behaviors. Endogenous opioid peptides and receptors are expressed in the BST, but their exact distribution is poorly characterized. The present study used in situ hybridization in order to characterize the endogenous opioid system of the BST, focusing on both enkephalin and dynorphin neuropeptides, as well as their respective receptors (mu, delta, and kappa opioid receptors). We report that preprodynorphin mRNA is observed in distinct nuclei of the BST, namely the fusiform, oval and anterior lateral nuclei. In contrast, there is a widespread expression of preproenkephalin mRNA in both anterior and posterior divisions of the BST. Similarly, mu and kappa opioid receptors are broadly expressed in the BST, whereas delta opioid receptor mRNA was observed only in the principal nucleus. For further characterization of enkephalin-expressing neurons of the BST, we performed a double fluorescent in situ hybridization in order to reveal the coexpression of enkephalin peptides and markers of GABAergic and glutamatergic neurons. Although most neurons of the BST are GABAergic, there is also a modest population of glutamatergic cells expressing vesicular glutamate transporter 2 (VGLUT2) in specific nuclei of the BST. Finally, we identified a previously unreported population of enkephalinergic neurons expressing VGLUT2, which is principally located in the posterior BST.     

Modulation of glutamatergic synaptic transmission in the bed nucleus of the stria terminalis

Glutamate, catecholamine and neuropeptide signaling within the bed nucleus of the stria terminalis (BNST) have all been identified as key participants in anxiety-like behaviors and behaviors related to withdrawal from exposure to substances of abuse. The BNST is thought to serve as a key relay between limbic cognitive centers and reward, stress and anxiety nuclei. Human studies and animal models have demonstrated that stressors and drugs of abuse can result in long term behavioral modifications that can culminate in psychological diseases such as addiction and post-traumatic stress disorder. The ability of catecholamines and neuropeptides to influence synaptic glutamatergic transmission (stemming from cognitive centers) within the BNST may have profound consequences over these behaviors. In this review we highlight studies examining synaptic plasticity and modulation of excitatory transmission within the BNST, emphasizing how such modulation may result in alterations in anxiety and reward related behavior.     

Nuclei-and condition-specific responses to pain in the bed nucleus of the stria terminalis

The bed nucleus of the stria terminalis (BST) is a basal forebrain structure considered to be part of a cortico-striato-pallidal system that coordinates autonomic, neuroendocrine and behavioural physiological responses. Recent evidence suggests that the BST plays a role in the emotional aspect of pain. The objective of the present study was to further understand the neurophysiological bases underlying the involvement of the BST in the pain experience, in both acute and chronic pain conditions. Using c-Fos as an indicator of neuronal activation, the results demonstrated that a single toe-pinch in rats produced nuclei-and condition-specific neuronal responses within the anterior region of the BST (antBST). Specifically, acute noxious stimulation increased c-Fos in the dorsal medial (dAM) and fusiform (FU) nuclei. Chronic neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve decreased the number of c-Fos positive cells following acute mechanical stimulation in the dAM and FU nuclei, and increased c-Fos immunoreactivity in the ventral medial (vAM) aspect of the BST. In addition, the results revealed a nuclei-specific sensitivity to the surgical procedure. Following noxious stimulation to animals that received a sham surgery, c-Fos immunoreactivity was blunted in the FU nucleus while it increased in the oval (OV) nucleus of the BST. Altogether, this study demonstrates that pain induces nuclei-and condition-specific neuronal activation in the BST revealing an intriguing supraspinal neurobiological substrate that may contribute to the physiology of acute nociception and the pathophysiology of chronic pain.     

Resting-state causal connectivity of the bed nucleus of the stria terminalis in panic disorder

Panic disorder (PD) is associated with anticipatory anxiety, a sustained threat response that appears to be related to the bed nucleus of the stria terminalis (BNST). Individuals with panic disorder may demonstrate significant differences in causal connectivity of the BNST in comparison to healthy controls. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant causal connectivity of the BNST in PD patients. 19 PD patients and 18 healthy controls (HC) matched for gender, age and education were included. Granger causality analysis (GCA) utilizing the BNST as a seed region was used to investigate changes in directional connectivity. Relative to healthy controls, PD patients displayed abnormal directional connectivity of the BNST including enhanced causal connectivity between the left parahippocampal gyrus and left BNST, the right insula and the right BNST, the left BNST and the right dorsolateral prefrontal cortex (dlPFC) and right BNST to the left and right dlPFC. Furthermore, PD patients displayed weakened causal connectivity between the right dlPFC and the left BNST, the left dlPFC and the right BNST, the left BNST and the left dorsomedial prefrontal cortex (dmPFC), right insula, right fusiform, and right BNST to the right insula. The results suggest that PD strongly correlates with increased causal connectivity between emotional processing regions and the BNST and enhanced causal connectivity between the BNST and cognitive control regions.

     

Plasma corticosterone responses to electrical stimulation of the bed nucleus of the stria terminalis

The effect of ventral septal stimulation on pituitary-adrenal function was assessed by evaluating plasma corticosterone obtained prior to and following sham or electrical stimulation of the bed nucleus of the stria terminalis (BNST) of female rats anesthetized with urethane (1.3 g X kg-1). Hippocampal EEG, ECG, heart rate, blood pressure and respiration were routinely monitored; timed blood samples (0.2 ml) for determining plasma corticosterone (RIA) were obtained from a catheterized tail artery. Samples were taken at 0.5 min prior to and at 5, 10, 15 and 30 min after initiation of stimulation. Whereas increased plasma corticosterone levels followed stimulation of the medial aspect of the BNST, lateral stimulation resulted in decreased plasma corticosterone levels. The overall increase in plasma corticosterone following medial stimulation was 24%; the overall decrease was 13%. The largest increase in plasma corticosterone (36%) occurred at 30 min poststimulation; the largest decrease (22%) occurred at 15 min. Stimulation of the most rostral aspect of the BNST produced plasma corticosterone responses similar to that observed following medial stimulation. In contrast, no changes in corticosterone levels were observed following either sham stimulation or stimulation of the corpus callosum, fornix or anterior commissure.     

Characterization of the bed nucleus of the stria terminalis in the forebrain of anuran amphibians

Major common features have been reported for the organization of the basal telencephalon in amniotes, and most characteristics were thought to be acquired in the transition from anamniotes to amniotes. However, gene expression, neurochemical, and hodological data obtained for the basal ganglia and septal and amygdaloid complexes in amphibians (anamniotic tetrapods) have strengthened the idea of a conserved organization in tetrapods. A poorly characterized region in the forebrain of amniotes has been the bed nucleus of the stria terminalis (BST), but numerous recent investigations have characterized it as a member of the extended amygdala. Our study analyzes the main features of the BST in anuran amphibians to establish putative homologies with amniotes. Gene expression patterns during development identified the anuran BST as a subpallial, nonstriatal territory. The BST shows Nkx2.1 and Lhx7 expression and contains an Islet1-positive cell subpopulation derived from the lateral ganglionic eminence. Immunohistochemistry for diverse peptides and neurotransmitters revealed that the distinct chemoarchitecture of the BST is strongly conserved among tetrapods. In vitro tracing techniques with dextran amines revealed important connections between the BST and the central and medial amygdala, septal territories, medial pallium, preoptic area, lateral hypothalamus, thalamus, and prethalamus. The BST receives dopaminergic projections from the ventral tegmental area and is connected with the laterodorsal tegmental nucleus and the rostral raphe in the brainstem. All these data suggest that the anuran BST shares many features with its counterpart in amniotes and belongs to a basal continuum, likely controlling similar reflexes, reponses, and behaviors in tetrapods.     

Activation of the bed nucleus of the stria terminalis increases gastric motility in the rat

The diencephalic bed nucleus of the stria terminalis is known to make direct, peptide-containing axonal connections with the brainstem dorsal vagal complex, i.e., the nucleus of the solitary tract and the dorsal motor nucleus of the vagus. Given these anatomical data, one would predict that the bed nucleus, like other forebrain nuclei with similar connections, should function to alter parasympathetic autonomic functions. To examine this possibility, we activated the bed nucleus via electrical microstimulation and glutamate microinjections while monitoring gastric motility with miniature extraluminal strain gauges. We found that activation of the bed nucleus produced an increase in gastric motility that was atropine sensitive. This finding raises the possibility that the bed nucleus may be a significant forebrain regulator of gastrointestinal function.     

Sex difference in the bed nucleus of the stria terminalis of the human brain.

A quantitative analysis of the volume of the darkly staining region of the posteromedial bed nucleus of the stria terminalis was performed on the brains of 26 age-matched male and female human subjects. We suggest the term "darkly staining posteromedial" component of the bed nucleus of the stria terminalis (BNST-dspm) to describe this sexually dimorphic region of the human brain. The volume of the BNST-dspm was 2.47 times greater in males than in females. This region in humans appears to correspond to an area of the bed nucleus of the stria terminalis in laboratory animals that exhibits volumetric and neurochemical sexual dimorphisms, concentrates gonadal steroids, and is anatomically connected to several other sexually dimorphic nuclei. Furthermore, the bed nucleus of the stria terminalis is involved in sexually dimorphic functions, including aggressive behavior, sexual behavior, and gonadotropin secretion, which are also influenced by gonadal steroids. Therefore, it is possible that in human beings as well, gonadal hormones influence the sexual dimorphism in the BNST-dspm and that this morphological difference, in part, underlies sexually dimorphic function.