It takes two: Bilateral bed nuclei of the stria terminalis mediate the expression of contextual fear, but not of moderate cued fear.

A growing body of research supports a prominent role for the bed nucleus of the stria terminalis (BST) in the expression of adaptive and perhaps even pathological anxiety. The traditional premise that the BST is required for long-duration responses to threats, but not for fear responses to distinct, short-lived cues may, however, be oversimplified. A thorough evaluation of the involvement of the BST in cued and contextual fear is therefore warranted. In a series of preregistered experiments using male Wistar rats, we first addressed the involvement of the BST in cued fear. Following up on earlier work where we found that BST lesions disrupted auditory fear while the animals were in a rather high stress state, we here show that the BST is not required for the expression of more specific fear for the tone under less stressful conditions. In the second part, we corroborate that the same lesion method does attenuate contextual fear. Furthermore, despite prior indications for an asymmetric recruitment of the BST during the expression of anxiety, we found that bilateral lesioning of the BST is required for a significant attenuation of the expression of contextual fear. A functional BST in only one hemisphere resulted in increased variability in the behavioral outcome. We conclude that, in animals that acquired a fear memory with an intact brain, the bilateral BST mediates the expression of contextual fear, but not of unambiguous cued fear.

Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

OBJECTIVE: Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. METHODS: Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. RESULTS: Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. CONCLUSION: Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

Intercalated and paracapsular cell islands of the adult rat amygdala: a combined rapid-Golgi, ultrastructural, and immunohistochemical account.

The anterior and rostral paracapsular intercalated islands (AIC and PIC, respectively) were studied in the context of the amygdaloid modulation of fear/anxiety using horizontal sections. The structural analysis carried out using silver-impregnated specimens revealed that the AIC is composed of tightly packed, medium-sized spiny neurons with distinct dendritic and axonal patterns that send projecting axons to the central nucleus of the amygdala. The AIC occupies a strategic position between the basolateral amygdaloid complex and the caudal limb of the anterior commissure from which it receives fibers en passage and axon terminals. Electron microscopic observation of terminal (i.e., synaptic) degeneration 72 h after the surgical interruption of the anterior commissure, confirms the synaptic interaction between the latter and the AIC neurons. These observations suggest that these islands may gate the activity of neurons from the contralateral basal forebrain and synchronize the anxiogenic output of both amygdalae. Immunohistochemical analysis indicated that, within the AIC and rostral PIC, the distance between tyrosine hydroxylase-immunoreactive terminals and the punctate dopamine D(1) receptor immunoreactivity, was in the micrometer range. These results indicate a short distance and a rapid extrasynaptic form of dopamine volume transmission mediated via D(1) receptors in the AIC and PIC which may enhance fear and anxiety by suppressing feed-forward inhibition in the basolateral and central amygdaloid nuclei. The strong suggestion for a commissural axon projection to the AIC documented here, coupled with the previous evidences indicting an isocortical and amygdalar contributions to the anterior commissure, opens the possibility that the AIC may be involved in decoding nerve impulses arising from both the ipsi- and contra-lateral forebrain to, in turn, modulate the homolateral amygdala.

Effects of BNST lesions in female rats on forced swimming and navigational learning.

The bed nucleus of the stria terminalis (BNST) in the forebrain shows sexual dimorphism in its neuroanatomical connectivity and neurochemical characteristics. The structure is involved in many behavioral and motivational phenomena particularly related to coping with stress. Female rats differ from males in responding to stressful situations such as forced swimming and navigational learning in the water maze. It was previously shown that bilateral damage to the BNST in male Wistar rats aggravated depression as measured by forced swim tests, but did not impair navigational learning in the water maze. The present study extended the findings to female rats demonstrating that bilateral electrolytic lesions of the BNST increased immobility and decreased climbing compared to sham-operated controls, but failed to affect performance in the water maze. Additionally, lesions did not alter behavior in the open field and the elevated plus-maze tests suggesting not only that the modulation of depression by BNST lesions is specific, but also providing support for the view that the BNST may not necessarily be critically involved in anxiety.

Safety of anterior commissure-posterior commissure-based target calculation of the subthalamic nucleus in functional stereotactic procedures.

The subthalamic nucleus (STN) is a common target of functional stereotactic surgeries. High-field magnetic resonance imaging and sophisticated computer systems provide precise identification of the nucleus location in stereotactic space. However, it is unclear what additional benefit these techniques provide over traditional anterior commissure-posterior commissure (AC-PC)-based standard atlas coordinate calculation methods based on the AC-PC plane. The accuracy of AC-PC-based standard atlas coordinate targeting of the STN using 1.5-tesla images compared with direct visualization of the nucleus on fused 3-tesla images was examined. A retrospective examination of stereotactic images from 20 patients (40 STN targets) who underwent deep brain stimulation for Parkinson's disease was undertaken at our institution. Two methods were used to identify the STN stereotactic coordinates: (1) an AC-PC-based standard atlas coordinate calculation obtained by a series of measurements using 1.5-tesla images, and (2) a computer workstation calculation using fused 3-tesla and 1.5-tesla images. Euclidean distances between two sets of coordinates of the same target were calculated in three dimensions. Differences along individual X, Y, and Z axes were analyzed to determine whether there was a greater difference in one direction than in another. Data from the right and left sides were pooled to increase the sample power. The anterior-posterior and lateral frame tilts were compared to X, Y, and Z differences to find a correlation using linear regression. Statistical analyses were performed. The accuracy of the position of the STN calculated with state-of-the-art imaging systems was not significantly better than that obtained using traditional AC-PC-based standard atlas coordinate calculation if the frame was aligned with the AC-PC plane. The mean difference was 0.45 mm, 0.72 mm, and 0.98 mm in the X, Y, and Z axes, respectively. Therefore, it is possible to effectively target the STN for stereotactic treatment of Parkinson's disease, for instance in a situation where expensive advanced technology is unavailable.

Attenuation of gonadal response to photostimulation following ablation of neurons in the lateral septal organ of chicks.

Many avian species in temperate zones respond to long photoperiods by showing recrudescence of gonads. Compelling evidence show that non-retinal, non-pineal photoreceptors exist in the avian brain. Within the ventral forebrain are specialized neurons that respond to light found in the medial portion of a circumventricular organ called the lateral septal organ (LSO). The objective of this study was to examine whether the integrity of the LSO was critical for rapid gonadal development in young male chicks placed under long day photostimulation. Birds were initially kept on a short photoperiod (LD 8:16) until 2 weeks of age, at which time bilateral electrolytic lesions were administered to the LSO. After surgery, birds were transferred to a long photoperiod (LD 16:8) and fed a chick starter diet containing 0.2% sulfamethazine (SMZ). The combination of a long day plus SMZ is known to stimulate sexual maturation in male chicks. In four separate experiments conducted to date, bilateral lesions directed to the LSO and lesions that missed and were placed caudal and ventral to the target resulted in a significant decrease in testes weight, compared to sham-operated controls (P<0.05). Results suggest that neurons in the LSO may be directly involved in responding to long photoperiods and stimulating gonadal development in broiler chicks.

Electrolytic lesions of the medial septum enhance latent inhibition in a conditioned taste aversion paradigm.

The effects of medial septal lesions on latent inhibition (LI) were assessed in a conditioned taste aversion paradigm. Animals were tested in a LI paradigm 2 weeks after receiving medial septal or sham lesions. The LI paradigm involved a pre-exposure phase in which water-deprived rats were allowed access to either water (non-pre-exposed; NPE) or 5% sucrose (pre-exposed; PE), followed by a conditioning phase in which animals were allowed access to sucrose and subsequently injected with lithium chloride, and a test phase in which animals were allowed access to both sucrose and water. LI was assessed by comparing the %-sucrose consumed in PE and NPE groups on the test day. There was a significantly greater LI effect in the lesion group than in the sham group, suggesting that electrolytic lesions to the medial septum can enhance LI in a CTA paradigm.

Hormonal regulation of hippocampal spine synapse density involves subcortical mediation.

It is well established that estrogen has positive effects on the density of pyramidal cell spines in the hippocampal CA1 subfield. This study explored whether afferent connections of the hippocampus that come from estrogen-sensitive subcortical structures, including the septal complex, median raphe and supramammillary area, play a role in this estrogen-induced hippocampal synaptic plasticity. These particular subcortical structures have major influences on hippocampal activity, including theta rhythm and long-term potentiation. The latter also promotes the formation of new synapses. All of the rats were ovariectomized; the fimbria/fornix, which contains the majority of subcortical efferents to the hippocampus, was transected unilaterally in each, and half of the animals received estrogen replacement. Using unbiased electron microscopic stereological methods, the CA1 pyramidal cell spine synapse density was calculated. In the estrogen-treated rats, contralateral to the fimbria/fornix transection, the spine density of CA1 pyramidal cells increased dramatically, compared to the spine density values of both the ipsilateral and contralateral hippocampi of non-estrogen-treated animals and to that of the ipsilateral hippocampus of the estrogen replaced rats. These observations indicate that fimbria/fornix transection itself does not considerably influence CA1 area pyramidal cell spine density and, most importantly, that the estrogenic effect on hippocampal morphology, in addition to directly affecting the hippocampus, involves subcortical mediation.

Cholinergic expression by a neural stem cell line grafted to the adult medial septum/diagonal band complex.

The potential of a neural stem cell line to acquire cholinergic characteristics was studied in transplants injected into the septum/diagonal band nuclei of young adult rats and mice. The stem cells integrated within the nuclei and survived for up to 9 months. Three methods were used to identify the grafted cells and to show differentiation into astrocytes and neurons. Enhanced survival of the stem cells occurred in the host brain with a previous lesion of the fimbria-fornix pathway. Differentiated cells acquired neuronal-like features including the expression of neurofilament subunits. In lesioned hosts, subpopulations of the grafted cells acquired a cholinergic neuronal phenotype and expressed choline acetyltransferase and the p75 neurotrophin receptor. Cells that developed into astrocytes were often associated with blood vessels and expressed glial fibrillary acidic protein. The results further exemplify the potential of stem cell lines and the property of site-specific differentiation when this line is transplanted to the cholinergic system of the adult brain.

SEK1/MKK4, c-Jun and NFKappaB are differentially activated in forebrain neurons during postnatal development and injury in both control and p75NGFR-deficient mice.

The common neurotrophin receptor (p75NGFR) can signal in vitro through activation of the c-Jun N-terminal kinase (JNK) pathway and nuclear translocation of NFKappaB. Activation of JNK and its substrate c-Jun can lead to apoptosis. We investigated these activities in vivo by comparing immunoreactivity for phosphorylated(p) SEK-1 (or MKK4, which activates JNK), c-Jun (ser63, ser73) and nuclear translocation of NFKappaB-p50 in tissue sections through the forebrain of control and p75NGFR-deficient mice. During postnatal development, SEK1p-immunoreactivity was detectable in p75NGFR-positive cholinergic neurons and p75NGFR-negative neurons throughout the forebrain in control mice. During development, few cells contained c-Junp, although many neurons contained c-Jun. No obvious c-Jun immunostaining was present in the adult forebrain. At any age, NFKappaB-p50 immunoreactivity was seen in nuclei of most cells throughout the forebrain. Following fimbria fornix transection in adult mice, few basal forebrain neurons contained SEK1p while many axotomized choline acetyltransferase (ChAT)-positive neurons contained c-Junp and nuclear NFKappaB-p50. The immunostaining patterns of SEK1p, c-Junp and NFKB during development and following injury were largely similar in p75NGFR-deficient mice. During development, cells throughout the forebrain had TdT-mediated dUTP-biotin nick end labelling (TUNEL)-labelling (a potential marker for apoptosis), however, their presence was not predicted by number of neurons stained for SEK1p or c-Junp. These results suggest that the expected activation of the JNK pathway by p75NGFR, as well as the expected relationship between SEK1 and downstream activation of c-Jun do not occur in the mammalian forebrain. Also, these results suggest that this activation does not necessarily lead to cell death.

D-cycloserine, a partial NMDA receptor-associated glycine-B site agonist, enhances reversal learning, but a cholinesterase inhibitor and nicotine has no effect.

The present study examined the efficacy of single and combined treatments with an anticholinesterase, tetrahydroaminoacridine, nicotine and a glycine-B site partial agonist, D-cycloserine, in alleviating the water maze reversal learning defect induced by a medial septal lesion. D-cycloserine (3 and 10 mg/kg) improved reversal learning. Tetrahydroaminoacridine (1 and 3 mg/kg) and nicotine (0.1 and 0.3 mg/kg) had no effect on reversal learning. A combination of tetrahydroaminoacridine 3 mg/kg or nicotine 0.3 mg/kg and D-cycloserine 10 mg/kg was not more effective than D-cycloserine 10 mg/kg alone in improving reversal learning. This suggests that stimulation of NMDA mechanisms may more effectively improve in medial septal-lesioned rats reversal learning processes than stimulation of cholinergic activity.

Does the bed nucleus of the stria terminalis mediate fear behaviors?

The bed nucleus of the stria terminalis (BNST) has been implicated in autonomic and hormonal reactions to fearful stimuli, but its role in behavioral reactions to these stressors is less clear. This is puzzling, because 2 closely related areas, the septum and the amygdala, have been repeatedly implicated in fear behaviors. To investigate further, the behavioral effects of BNST lesions were compared to those of septal and amygdaloid lesions in 2 models of rat anxiety: the plus-maze and shock-probe tests. Septal lesions inhibited rats' open-arm avoidance in the plus-maze and suppressed burying of the shock-probe, whereas amygdaloid lesions specifically inhibited shock-probe avoidance. However, BNST lesions produced none of these anti-fear effects; thus, its involvement in the behavioral expression of fear is questionable.

Role of the septum in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex.

Intracerebroventricular administration of corticotropin-releasing hormone (CRH) elicits a constellation of behavioral, autonomic, and endocrinological changes typically observed in stress. One of the behavioral changes after intracerebroventricular CRH is a profound increase of startle amplitude (CRH-enhanced startle). The present study examined the role of the septum in CRH-enhanced startle. The septum has direct and indirect connections to the amygdala and inhibits the amygdala. Electrophysiological data show that CRH in the septum is inhibitory. Therefore, it has been hypothesized that intracerebroventricular CRH inhibits the septum, which in turn disinhibits the amygdala, resulting in a constellation of changes via activation of amygdala efferent targets. In testing this hypothesis, it was found that electrolytic lesions of the medial septum, but not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing chemical lesions of the medial septum did not block CRH-enhanced startle, suggesting that the blockade seen with the electrolytic lesions was caused by damage to fibers of passage. A major fiber bundle passing through the medial septum is the fornix, the primary efferent pathway for the hippocampus. Fimbria transection blocked CRH-enhanced startle almost completely, whereas the large electrolytic lesions of the dorsal hippocampus did not block CRH-enhanced startle. Taken together, these data suggest that perhaps the ventral hippocampus and its efferent target areas, which communicate via the fimbria, may be critically involved in CRH-enhanced startle.

Modulation of hippocampal acetylcholine release after fimbria-fornix lesions and septal transplantation in rats.

Female Long-Evans rats sustained electrolytic lesions of the fimbria and the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts of fetal septal cell suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in the hippocampus of sham-operated, lesion-only and grafted rats was measured by microdialysis. The extent of cholinergic (re)innervation was determined by acetylcholinesterase (AChE) staining and densitometry. In both lesion-only and grafted rats, the ratio of ACh release to AChE staining intensity was increased as compared to sham-operated rats, indicating a loss of endogenous inhibitory mechanisms. Scopolamine (0.5 mg/kg i.p.), a muscarinic antagonist, increased ACh release in all treatment groups. 8-OH-DPAT (0.5 mg/kg s.c.), an agonist at serotonergic 5HT1A-receptors, induced an increase of hippocampal ACh release in sham-operated rats. This effect was lost in lesion-only rats, but was fully restored by neuronal grafting. As 8-OH-DPAT influences hippocampal ACh release by a postsynaptic action, this finding indicates that the host brain exerts a serotonergic influence on the grafted cholinergic neurons.

[An analysis of the seasonal differences in the reaction of the hypothalamo-hypophyseal-ovarian system to the light regimen of the housing of animals after destruction of the lateral septal nucleus]. / Analiz sezonnykh vidminnostei v reaktsiï hipotalamo-hipofizarno-iaiechnykovoï systemy na svitlovyi rezhym utrymannia tvaryn pislia zruinuvannia lateral'noho iadra perehorodky mozku.

The investigation of the lateral septal nucleus (LSN) destruction participation in biorhythmological processes of the morphofunctional condition of the female genital apparatus of female rats was made in the experiments of juvenile female rats, i.e. such which are caused by the change of seasons of the year and light condition. It is shown that the reaction of the hypothalamo-hypophysis-ovary system (HHOS) on the changes of light conditions depends on the season of the year: in spring the regular darkness lends to the negative consequences in the sexual system, and in summer and autumn on the contrary, makes in more active. Regular lighting stimulates the HHOS only in spring. The realisation of photoperiodic processes in HHOS may be possible only in the presence of intact LSN. It is exposed that the reaction of HHOS of animals with destructive LSN in all seasons of the year and under different light conditions are opposite to those which take place in female rats with intact LSN.

Fimbria-fornix transections selectively down-regulate subtypes of glutamate transporter and glutamate receptor proteins in septum and hippocampus.

The effects of CNS axotomy on glutamate transporter and glutamate receptor expression were evaluated in adult rats following unilateral fimbria-fornix transections. The septum and hippocampus were collected at 3, 7, 14, and 30 days postlesion. Homogenates were immunoblotted by using antibodies directed against glutamate transporters (GLT-1, GLAST, and EAAC1) and glutamate receptors (GluR1, GluR2/3, GluR6/7, and NMDAR1), and they were assayed for glutamate transport by D-[3H]aspartate binding. GLT-1 was decreased at 7 and 14 days postlesion within the ipsilateral septum and at 7 days postlesion in the hippocampus. GLAST was decreased within the ipsilateral septum and hippocampus at 7 and 14 days postlesion. No postlesion alterations in EAAC1 immunoreactivity were observed. D-[3H]Aspartate binding was decreased at 7, 14, and 30 days postlesion within the ipsilateral septum and 14 days postlesion in the hippocampus. GluR2/3 expression was down-regulated at 30 days postlesion within the ipsilateral septum, whereas GluR1, GluR6/7, and NMDAR1 immunoreactivity was unchanged. In addition, no alterations in glutamate receptor expression were detected within hippocampal homogenates. This study demonstrates a selective down-regulation of primarily glial, and not neuronal, glutamate transporters and a delayed, subtype-specific down-regulation of septal GluR2/3 receptor expression after regional deafferentation within the CNS.

Downregulation of muscarinic- and 5-HT1B-mediated modulation of [3H]acetylcholine release in hippocampal slices of rats with fimbria-fornix lesions and intrahippocampal grafts of septal origin.

Adult Long-Evans female rats sustained electrolytic fimbria-fornix lesions and, two weeks later, received intrahippocampal suspension grafts of fetal septal tissue. Sham-operated and lesion-only rats served as controls. Between 6.5 and 8 months after grafting, both the [3H]choline accumulation and the electrically evoked [3H]acetylcholine ([3H]ACh) release were assessed in hippocampal slices. The release of [3H]ACh was measured in presence of atropine (muscarinic antagonist, 1 microM), physostigmine (acetylcholinesterase inhibitor, 0.1 microM), oxotremorine (muscarinic agonist, 0.01 microM-10 microM), mecamylamine (nicotinic antagonist, 10 microM), methiothepin (mixed 5-HT1/5-HT2 antagonist, 10 microM), 8-OH-DPAT (5-HT1A agonist, 1 microM), 2-methyl-serotonin (5-HT3 agonist, 1 microM) and CP 93129 (5-HT1B agonist, 0.1 microM-100 microM), or without any drug application as a control. In lesion-only rats, the specific accumulation of [3H]choline was reduced to 46% of normal and the release of [3H]ACh to 32% (nCi) and 43% (% of tissue tritium content). In the grafted rats, these parameters were significantly increased to 63%, 98% and 116% of control, respectively. Physostigmine reduced the evoked [3H]ACh release and was significantly more effective in grafted (-70%) than in sham-operated (-56%) or lesion-only (-54%) rats. When physostigmine was superfused throughout, mecamylamine had no effect. Conversely, atropine induced a significant increase of [3H]ACh release in all groups, but this increase was significantly larger in sham-operated rats (+209%) than in the other groups (lesioned: +80%; grafted: +117%). Oxotremorine dose-dependently decreased the [3H]ACh release, but in lesion-only rats, this effect was significantly lower than in sham-operated rats. Whatever group was considered, 8-OH-DPAT, methiothepin and 2-methyl-serotonin failed to induce any significant effect on [3H]ACh release. In contrast, CP 93129 dose-dependently decreased [3H]ACh release. This effect was significantly weaker in grafted rats than in the rats of the two other groups. Our data confirm that cholinergic terminals in the intact hippocampus possess inhibitory muscarinic autoreceptors and serotonin heteroreceptors of the 5-HT1B subtype. They also show that both types of receptors are still operative in the cholinergic terminals which survived the lesions and in the grafted cholinergic neurons. However, the muscarinic receptors in both lesioned and grafted rats, as well as the 5-HT1B receptors in grafted rats show a sensitivity which seems to be downregulated in comparison to that found in sham-operated rats. In the grafted rats, both types of downregulations might contribute to (or reflect) an increased cholinergic function that results from a reduction of the inhibitory tonus which ACh and serotonin exert at the level of the cholinergic terminal.

Fate of GABAergic septohippocampal neurons after fimbria-fornix transection as revealed by in situ hybridization for glutamate decarboxylase mRNA and parvalbumin immunocytochemistry.

Many septohippocampal neurons are GABAergic and are affected by transection of the fimbria-fornix, like the septohippocampal cholinergic cells. Here we have studied the changes that occur in GABAergic septohippocampal neurons following fimbria-fornix transection. For labeling of septohippocampal projection neurons, adult Sprague-Dawley rats received injections of the fluorescent tracer Fluoro-Gold into the hippocampus 1 week prior to bilateral transection of the fimbria-fornix. After axotomy, rats were allowed to survive for varying periods ranging from 3 weeks to 18 months. Following fixation of the animals, sections through the septal region were either stained by in situ hybridization for glutamate decarboxylase (GAD) mRNA or immunostained for parvalbumin (PARV), which is known to be present in GABAergic septohippocampal neurons. In situ hybridization for GAD mRNA revealed no statistically significant changes in cell number 3 weeks and 6 months postlesion. In contrast, PARV-immunoreactive neurons were reduced to 35% of control 3 weeks postlesion. This value increased to 66% after 6 months of survival. As seen in the electron microscope, axotomized PARV-positive neurons exhibited characteristics of vital cells. Most neurons contained lysosomes associated with Fluoro-Gold, resulting from retrograde labeling prior to fimbria-fornix transection. We conclude that mainly PARV-containing GABAergic neurons in the medial septal nucleus (MS) project to the hippocampus and are thus heavily affected by the lesion but are able to survive and restore the synthesis of PARV. The lack of significant changes in the number of GAD mRNA-expressing cells is explained by the presence of numerous GABAergic MS neurons not projecting to the hippocampus.

Septal lesions block sympathetic activation following frontal cortex stimulation in the rat.

The rates of oxygen consumption, colonic and interscapular brown adipose tissue temperature, and discharge of sympathetic nerves innervating the same tissue were recorded before and after orbital frontal cortex stimulation in three groups of rats. These groups consisted of animals with electrolytic lesions of the nucleus medialis septi, with lesions of nucleus lateralis septi or with sham lesions. The values of all the variables considered were similar during the pre-stimulation time in the three groups of rats. There was an increase in all the parameters in sham-lesioned animals after electrical stimulation, while no changes were found in the two groups of injured rats. The results showed that the frontal cortex is involved in the control of thermogenesis through the activation of the sympathetic nervous system. Medial and lateral septal nuclei, in spite of their neurochemical and pharmacological differences, share a common role in the pathway from the frontal cortex to the hypothalamic area and the amygdala, which in turn drive the sympathetic nervous system.

Naloxone and initial estrogen action to induce lordosis in ovariectomized rats: the effect of a cut between the septum and preoptic area.

The effects of intra-third-ventricular (ITV) injection of naloxone (NLX), an opioid receptor antagonist, on lordosis behavior were studied in ovariectomized female rats given a horizontal half-circle cut located just above the anterior commissure (ARD) and subcutaneously (s.c.) treated with estradiol benzoate (EB) and progesterone (Prog). In ARD-sham control animals, lordosis quotient (LQ) was 78.8 +/- 4.2% (SE,n = 8). LQ (48.3 +/- 7.2%, SE, n = 8) in the ARD-sham rats significantly decreased with the ITV injection of NLX at the time of s.c. EB-priming. In contrast, lordosis reflex in the ARD-operated animals was maximally facilitated (sham versus ARD, P < 0.01). LQ in the ARD-operated rats did not decrease with the ITV injection of NLX at the s.c. EB-priming. The present results suggest that the opioidergic systems modulate an initial phase of estrogen action to induce lordosis and play a part in neural input from the forebrain structures to regulate female sexual receptivity.