Supracallosal longitudinal fiber bundle: Heterotopic cingulum,dorsal fornix or Probst bundle?

A thick longitudinal fiber bundle found within the dorsal corpus callosum in two unrelated adults (in a micrencephalic female patient and incidentally in another male patient) is considered to be a congenital aberrant cingulum. Agenesis or apparent hypoplasia of the indusium griseum of the limbic‐cingular system as an accompanying finding in the present cases may support this hypothesis. The dorsal fornix and Probst bundle are discussed in terms of differential diagnosis, although there was no further support for this possibility. The hyperplastic dorsocallosal gray substance is excluded.     

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.     

The source of origin of PACAP- and VIP-immunoreactive fibers in the laterodorsal division of the bed nucleus of the stria terminalis in the rat

The bed nucleus of the stria terminalis (BSTL), which is known to be involved in the modulation of stress responses, exhibits a dense network of pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) immunoreactive (ir) fibers. The origin of the PACAP-ir fibers is unknown, and the origin of the VIP-ir fibers remains uncertain. The most important brain regions connected to the BSTL are the amygdaloid nuclei, the paraventricular and ventromedial hypothalamic nuclei, mesencephalic periaqueductal grey, the dorsal and linear raphe nuclei, the parabrachial nucleus, and the dorsal vagal complex. After microinjecting cholera toxin B subunit (CTB) in the BSTL as a retrograde tracer, neurons were double labeled for CTB and PACAP or VIP immunohistochemistry and the cells from which the PACAP- and VIP-ir fiber networks in the BSTL originated were identified. Cholera toxin B subunit labeled and VIP-ir cells were found in the mesencephalic periaqueductal grey and the dorsal and linear raphe nuclei, but no double labeled cells were seen in the amygdaloid nuclei or the hypothalamic region. CTB- and PACAP-ir neurons were observed in the paraventricular nucleus and the dorsal vagal complex. No double labeled perikarya were seen in the parabrachial nucleus or in the amygdaloid nuclei.     

Experimental immunohistochemical studies on the amygdalofugal peptidergic (substance P and somatostatin) fibers in the stria terminalis of the rat

The amygdalofugal substance P (SP) and somatostatin (SRIF) neuron systems in the stria terminalis (ST) were investigated by means of the indirect immunofluorescence technique of Coons. SP- and SRIF-positive cells were mainly located in the area (Amc) between the central (ac) and medial (am) amygdaloid nuclei. Some extended medially into the am and laterally into the ac. Destruction of the Amc resulted in a marked reduction of SP- and SRIF-positive fibers in the ST. Furthermore, a substantial decrease in SP-positive fibers was seen in the dorsal part of the bed nucleus of the ST (stb), there was a small decrease in the SP-positive fibers in the lateral hypothalamus (LH), a significant decrease in the SRIF-positive fibers in the lateroventral part of the anterior hypothalamic nucleus (lvAH), and a small decrease in the SRIF-positive fibers in the LH. These facts indicate that the origins of a number of SP- and SRIF-positive fibers are the Amc and that the amygdalofugal SP pathway in the ST innervates stb and LH and the amygdalofugal SRIF pathway in the ST projects to lvAH and LH.     

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)     

Substance P in the amygdaloid complex, bed nucleus and stria terminalis of the rat brain

Radioimmunoassay and immunohistochemical techniques have demonstrated the presence of substance P in the medial and central nuclie of the amygdala and the bed nucleus of the stria terminalis. Hemisections and micro-knife cuts transecting the anterior, posterior, medial, lateral and ventral connections to the amygdala did not modify the content of substance P in the amygdala. In addition knife cuts totally isolating the medial amygdaloid nucleus from lateral and anterior-posterior connections did not reduce the substance P content of the medial nucleus, but produced a 70% reduction in the substance P content of the central nucleus. These results suggest that substance P containing neurones in the medial and central amygdaloid nuclei do not receive substance P projections originating outside the amygdala. However, there appears to be a short substance P projection from the medial nucleus to the central nucleus.     

The projection field of the stria terminalis in the rat brain. An experimental study

The problem of the stria terminalis projection field has been examined by use of two versions of the cupric-silver technique as well as variations of the Fink-Heimer and Nauta-Gygax techniques applied to material fixed under different conditions using brains from very young rats surviving 30 hours to four days after production of lesions at different levels of the course of the stria terminalis and related structures. The findings are as follows:

• (1) A dorsal subventricular portion of the stria terminalis divides into retrocommissural and supracommissural contingents which together account for degenerating terminals seen in the ipsilateral bed nuclei of the stria terminalis and of the anterior commissure, and in the medial preoptic-hypothalamic junction area. The supracommissural bundle also disseminates into the laterobasal septum, nucleus accumbens, olfactory tubercle, the posterior and medial divisions of the anterior olfactory nucleus, and the granular layer of the accessory olfactory bulb. Additional fibers end in the paucicellular capsule of the ventromedial hypothalamic nucleus, also in a small lateral parvocellular tuberal nuclear area, and throughout the premammillary nuclei. A small truly commissural division of the dorsal component was traced to the contralateral cortical amygdaloid nucleus and to small clusters of medial amygdaloid cells.
• (2) A ventral juxtacapsular portion of the stria terminalis was traced to the ipsilateral strial bed nucleus, medial preoptic-hypothalamic junction area, the entire ventromedial hypothalamic nucleus, the lateral tuberal area and the premammillary nuclei. The lateralmost fibers of the dorsal strial component as well as those of the ventral component which lie lateral to the “commissural bundle” appear to terminate exclusively in the lateral portions of the bed nucleus of the stria.
• (3) A “commissural bundle” or component, after crossing the midline in the anterior commissure, ends in the bed nucleus of the posterior limb of the latter, in the olfactory tubercle, prepiriform cortex, lateral amygdaloid nucleus and the strial bed nucleus. It is thus a decussation rather than a commissure. No contribution from stria terminalis to stria medullaris could be identified.

     

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.     

The bed nucleus of the stria terminalis and immobilization-stress: Unit activity,escape behaviour,and gastric pathology in rats

Multiple unit-activity in the bed nucleus of the stria terminalis was increased or decreased, relative to baselines, during physical restraint in rats. Changes in unit-activity were also obtained by presenting an auditory stimulus that had been paired with the immobilization treatment. The animals escaped from that stimulus in behavioural tests, and bilateral lesions in the bed nucleus reduced the latencies of escape responses. The lesion also increased the severity of restraint-induced mucosal erosions. The latter effect was most pronounced when the damage was in the lateral portion of the bed nucleus. It was concluded that the bed nucleus of the stria terminalis is part of a coping system which responds when the organism is placed in a stressful situation.     

Neuropeptide Y in the stria terminalis: evidence for an amygdalofugal projection

Lesions of the stria terminalis in the rat brain indicate that neuropeptide Y, a recently isolated peptide of the pancreatic polypeptide family, projects rostrally in an efferent pathway from the amygdaloid complex. Marked depletions of NPY-immunoreactivity observed by immunocytochemistry were apparent in the laterobasal septum and suprachiasmatic nucleus of the hypothalamus, but most markedly in rostrolateral regions of the bed nucleus of the strial terminalis.     

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.     

Bed nucleus of the stria terminalis and the cardiovascular responses to chemoreflex activation

Several studies from our group have indicated that the BNST play an important role in baroreflex modulation. However, the involvement of the BNST in the chemoreflex activity is unknown. Thus, in the present study, we investigated the effect of the local bed nucleus of stria terminalis (BNST) neurotransmission inhibition by bilateral microinjections of the non-selective synaptic blocker cobalt chloride (CoCl(2)) on the cardiovascular responses to chemoreflex activation in rats. For this purpose, chemoreflex was activated with KCN (i.v.) before and after microinjections of CoCl(2) into the BNST. Reversible BNST inactivation produced no significant changes in the magnitude and durations of both pressor and bradycardic responses to intravenous KCN infusion. These findings suggesting that BNST neurotransmission have not influence on both sympathoexcitatory and parasympathoexcitatory components of the peripheral chemoreflex activation.     

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.     

Angiotensin II receptor binding sites in the ventral portion of the bed nucleus of the stria terminalis are reduced by interruption of the medial forebrain bundle

Many techniques have been utilized to discern the localization of angiotensin II (Ang II) receptors to specific cellular components (glia, neuronal cell bodies and nerve terminals) in the brain. In the present study, we used lesioning techniques to localize Ang II receptors to cellular components in the rat forebrain. In the first experiment, axons ascending to the hypothalamus and forebrain from neurons in the brainstem were destroyed by unilaterally cutting the medial forebrain bundle (MFB). In the second experiment, a single injection of the neurotoxin, ibotenic acid, was injected unilaterally into the ventral portion of the bed nucleus of the stria terminalis (BSTV) to destroy neuronal cell bodies, thus determining if Ang II receptors are present on neuronal cell bodies. In both experiments, the animals were sacrificed after two weeks recovery and the brains processed for in vitro receptor autoradiography using -sar¹,ile⁸ Ang II (-SI Ang II). Unilateral knife-cut lesions of the MFB caused a significant reduction in -SI Ang II binding in the BSTV (30±6%) and the piriform cortex (PC; 26±4%) ipsilateral to the knife cut. Unilateral injection of the neurotoxin into the BSTV failed to alter -SI Ang II binding in this nucleus. These experiments suggest that at least a subpopulation of Ang II receptors in the BSTV and PC are located on terminals of neurons that have their cell bodies in the brainstem and their axons in the MFB.     

Effects of D-Ala2-Met5-enkephalinamide microinjections placed into the bed nucleus of the stria terminalis upon affective defense behavior in the cat

This study examined the effects of intracerebral injections of D-Ala2-Met5-enkephalinamide (DAME) upon hypothalamically elicited hissing behavior in the cat. The bed nucleus of the stria terminalis (BNST) was selected for investigation because of its anatomical connections with the medial hypothalamus, its relatively high concentrations of enkephalins and opiate receptors and its demonstrated ability to modulate hypothalamically elicited aggressive reactions in the cat. DAME microinjected into the BNST in 1.0 or 10.0 micrograms/0.5 microliter quantities resulted in significant dose dependent increases in mean latencies for elicitation of the hissing response. Suppression of hissing following the 1.0 microgram dose of DAME was selectively diminished by prior administration of naloxone. These findings suggest that the opiate receptors within the BNST play a role in the regulation of the hissing component of hypothalamically elicited affective defense behavior.