Lesions of the stria terminalis attenuate the amnestic effect of amygdaloid stimulation on avoidance responses

The present study investigated the involvement of two amygdala pathways, the stria terminalis (ST) and the ventral amygdalofugal pathway (VAF), in the effect of post-training electrical stimulation of the amygdala on retention. Rats with implanted amygdaloid electrodes and ST lesions, VAF transections or sham pathway operations, were trained on an inhibitory avoidance task and an active avoidance task. Electrical stimulation of the amygdala was given immediately after training and retention was tested 24 h later. In rats with sham ST lesions, post-training amygdaloid stimulation impaired retention in both tasks. Lesions of the ST did not significantly affect retention in the unstimulated rats. However, the ST lesions attenuated the amnestic effect of amygdaloid stimulation. In rats with sham VAF transections, stimulation of the amygdala impaired retention in the inhibitory avoidance task but enhanced retention in the active avoidance task. Transecting the VAF impaired retention performance of the unstimulated rats in the inhibitory avoidance task. However, the VAF transections did not alter the effect of amygdaloid stimulation: in both tasks, the retention performance of stimulated rats with VAF transections did not differ from that of stimulated rats with sham transections. These findings suggest that the ST may be involved in mediating the influences of the stimulated amygdala in modulating memory storage processing in the brain.     

Post-training amygdaloid lesions impair retention of an inhibitory avoidance response

The study examined the effect of pre- and post-training bilateral amygdaloid lesions on retention of a one-trial inhibitory avoidance response. Groups of rats, including unimplanted controls and implanted controls, were trained and tested for retention at 4, 7 or 12 days following training. The lesions were made at one of several intervals before or after training: 2 days before, immediately after, or 2, 5 or 10 days after. At all retention intervals the retention of implanted controls was poorer than that of unimplanted controls and, in comparison with both control groups, the retention of animals lesioned before training was impaired. Retention was also impaired by the post-training lesions. The degree of impairment varied with the interval between the training and the lesion: lesions made within 2 days following training impaired retention, while lesions made 10 days following training had no impairing effect. These findings suggest that posttraining lesions of the amygdala affect retention by impairing time-dependent processes involved in memory storage. With a sufficiently long training-lesion interval (10 days) an intact amygdala is not essential for retention.     

Peripheral epinephrine modulates the effects of post-training amygdala stimulation on memory

The present study investigated the role of adrenal epinephrine in the memory modulatory effects of post-training amygdala stimulation. Adrenal demedullated (ADMX) or sham demedullated (SHAM) rats received electrical stimulation of the amygdala immediately after training on inhibitory and active avoidance tasks. With both tasks, the stimulation impaired retention only in the rats with intact adrenal medullae: the retention performance of the ADMX in the rats with intact adrenal medullae: the retention performance of the ADMX rats given post-training stimulation was better than that of the unstimulated ADMX group with implanted electrodes. However, ADMX rats given post-training epinephrine (1.0 mg/kg, s.c.) immediately before the amygdala stimulation had retention deficits comparable to those of the SHAM group given amygdala stimulation. If epinephrine was administered a short time after rather than before the post-training amygdala stimulation, retention of the ADMX animals was not impaired. The findings are interpreted as indicating that circulating epinephrine present at the time of amygdala stimulation modulates the effects of amygdala stimulation on memory.     

Stress shifts the response of the bed nucleus of the stria terminalis to an anxiogenic mode

The bed nucleus of the stria terminalis (BNST) is critically implicated in anxiety behavior and control of the hypothalamus–pituitary–adrenal axis. Having previously shown that chronic stress triggers dendritic/synaptic remodeling in specific nuclei of the BNST, we characterised the pattern of activation of neurons within different regions of the BNST under basal conditions and after an anxiogenic stimulus in control and stressed rats. Under basal conditions, stressed, but not control, animals displayed increased cFOS expression in the dorsomedial nucleus and decreased activation of the principal nucleus. This pattern resembled that observed in controls that had been exposed to the anxiogenic stimulus. Subsequent analysis of various BNST subnuclei revealed differential patterns of gene expression in controls and stressed animals. We found decreased levels of corticotropin‐releasing hormone 1 receptor mRNA expression in the dorsomedial and fusiform nuclei, and a global increase in the levels of corticotropin‐releasing hormone 2 receptor in the principal nucleus. In addition, we found subnuclei‐specific increases in GABA_A and NR2B receptors in stressed animals, which suggest changes in the GABAergic and glutamergic innervation of the BNST. Importantly, these findings were associated with increased anxiety‐like behavior and impaired control of the hypothalamus–pituitary–adrenal axis in stressed animals. In summary, these data reveal that chronic stress shifts the pattern of response of the BNST to an anxiogenic mode and provide new information on the underlying mechanisms of the stress‐induced hypercorticalism and hyperanxious status.     

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.     

The effect of castration on stria terminalis neurone absolute refractory periods using different antidromic stimulation loci

Iontophoresis and chronic micropipette implants were compared for delivery of retrograde fluorescent tracers. Injection sizes and retrograde transport were similar, but implants were more frequently successful than iontophoresis.     

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.     

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.     

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.     

Ventromedial nucleus of the hypothalamus: convergent excitatory and inhibitory responses to fimbria and stria terminalis stimulation

Field and extracellular unitary potentials were recorded in the ventromedial nucleus of the hypothalamus (VMH) of urethane-anesthetized rabbits after stimulation of the fimbria and stria terminalis. Stimulation of the lateral portion of the fimbria, which carries fibers from the ventral subiculum of the hippocampal formation, evoked a two-component response. An early excitatory response, with an average latency of 10 msec, predominated along the lateral margins of the VMH. A later inhibitory potential with an average latency of 15 msec was seen predominantly within the central portions of the VMH. Stimulation of the dorsal component of the stria terminalis produced two similar response patterns: an early excitatory response with an average latency of 16 msec, followed by an inhibitory potential with an average latency of 25 msec. The topographical distribution of these two components of the response was nearly identical to that produced by lateral fimbria stimulation. In contrast, stimulation of the ventral component of the stria terminalis evoked a simple excitatory response with an average latency of 10 msec which was maximal within the core of the VMH. Extracellular unitary recordings showed that the early negativity associated with stimulation of each of these three pathways reflects a monosynaptic excitation of VMH cells and that there was convergence of the three excitatory inputs at the single cell level.     

Electrical activity recorded from thin sections of the bed nucleus of the stria terminalis, and the effects of neurotensin

Effects of neurotensin on neurons in the bed nucleus of the stria terminalis (BST) were studied in vitro in thin brain sections of the guinea pig. Electrical stimulation to the stria terminalis (ST) elicited a negative field potential in the BST. The field potential was markedly suppressed in the medium containing Ca2+ at a low concentration of Mg2+ at a high concentration. BST neurons discharged in response to ST stimulation. Some of them also fired spontaneously. Neurotensin excited about two-thirds of BST neurons at concentrations of 0.35-35 nM. This excitation was not blocked when synaptic transmission was blocked in a medium containing Ca2+ in a low concentration and Mg2+ in a high concentration. These observations suggest that neurotensin is an excitatory transmitter or modulator in the amygdalo-BST projection.     

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.     

The memory-modulatory effects of glucocorticoids depend on an intact stria terminalis

This study examined the effects of stria terminalis (ST) lesions on glucocorticoid-induced modulation of memory formation for inhibitory avoidance training and spatial learning in a water maze. Systemic (s.c.) posttraining injections of the glucocorticoid receptor agonist dexamethasone (0.3 or 1.0 mg/kg) enhanced memory for inhibitory avoidance training in rats with sham ST lesions. Removal of the adrenal glands (adrenalectomy; ADX) significantly impaired spatial memory in a water maze, and immediate posttraining injections of dexamethasone (0.3 mg/kg) attenuated the memory impairment. Bilateral lesions of the ST did not significantly affect retention of these two tasks. However, ST lesions did block the effects of short-term ADX and dexamethasone administration on memory for both tasks. These results are similar to those of previous experiments examining the effects of lesions of the basolateral nucleus of the amygdala on the glucocorticoid-induced modulation of memory for both tasks. These findings suggest that the integrity of the ST, which connects the amygdala with other brain structures, is essential for the modulating effects of glucocorticoids on memory storage.     

Circulating angiotensin II activates neurones in circumventricular organs of the lamina terminalis that project to the bed nucleus of the stria terminalis

The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo- and magnocellular divisions of the paraventricular nucleus. Fos-labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB-gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double-labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.     

Neurons of the bed nucleus of the stria terminalis: A golgi study in the rat

Neuronal morphology in the bed nucleus of the stria terminalis (BST) was studied using Golgi techniques. The principal neurons of the lateral subdivision of BST have ovoid perikarya and 4–5 dendrites that branch several times and exhibit a dense covering of spines. Adjacent to the internal capsule is a small region, termed the “juxtacapsular subdivision” of BST, that consists of small, spiny cells. Neurons of the medial subdivision of BST have ovoid perikarya and 2–3 dendrites that branch sparingly. Dendritic spine density varies from sparse to moderate. Dendrites in the dorsocaudal portion of the medial subdivision extend into a cell-sparse zone adjacent to the lateral ventricle. Cells in the lateral portion of the preoptic continuation of BST have dendrites oriented perpendicular to fibers of the stria terminalis which traverse this area while medially located cells are oriented parallel to fibers of the stria. Axons of BST neurons emit collaterals that arborize modestly near the cell of origin. Neurons in the lateral and medial subdivisions of BST resemble, respectively, cells in the lateral and medial subdivisions of the central amygdaloid nucleus. Neurons in the juxtacapsular subdivision of BST are similar to neurons of the intercalated masses of the amygdala.     

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.     

A pilot study of bed nucleus of the stria terminalis deep brain stimulation in treatment-resistant depression

Background

Studies are increasingly investigating the therapeutic effects of deep brain stimulation (DBS) applied to a variety of brain regions in the treatment of patients with highly treatment refractory depression. Limited research to date has investigated the therapeutic potential of DBS applied to the Bed Nucleus Of Stria Terminalis (BNST).

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.