Lateral Septal Area Research Articles

Patterns of direct projections from the hippocampus to the medial septum-diagonal band complex: Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with immunohistochemistry of choline acetyltransferase

The projections from the Ammon's horn to the cholinergic cell groups in the medial septal and diagonal band nuclei were investigated with anterograde tracing of Phaseolus vulgaris leucoagglutinin combined with immunocytochemical detection of choline acetyltransferase, in the rat. Tracer injections were placed into various fields of the septal and temporal parts of the Ammon's horn (CA1–3). These injections revealed differential distributions of Phaseolus vulgaris leucoagglutinin-labeled projections in both the lateral septal area and the medial septum-diagonal band complex. In addition to the labeling of dense axonal networks in the lateral septal area, significant numbers of arborizing fibers were labeled in the medial septal and diagonal band nuclei, in particular after tracer injections into the fields CA2–3. The distributions of the projections to the medial septum-diagonal band complex arising from the septal portion of fields CA1 and CA2–3 are similar. In contrast, the septal part and temporal portion of field CA3 project in a topographically differentiated manner to the medial septum and nuclei of the diagonal band. The septal pole of the Ammon's horn innervates the dorsal and medial parts of the medial septal nucleus and the anterior and dorsal parts of the vertical limb of the diagonal band. Axons of the temporal pole of the hippocampus reach the lateral and ventral parts of the medial septum and the intermediate, caudal and ventral parts of the vertical limb of the diagonal band. These results demonstrate direct feedback projections of the Ammon's horm to the medial septumdiagonal band complex, which show a topographic organization mainly as a function of the septotemporal level of the hippocampus. Within the medial septal and diagonal band nuclei, the labeled varicosities are formed in close proximity to the cell bodies and dendrites of the cholinergic neurons.

Catecholaminergic, GABAergic, and hippocamposeptal innervation of gabaergic “somatospiny” neurons in the rat lateral septal area

This study deals with the neurochemical characterization of the rat lateral septal area (LSA) somatospiny neurons and their innervation by hippocamposeptal, catecholaminergic, and GABAergic fibers. Electron microscopic single and double immunostaining methods were used to label catecholaminergic fibers and GABAergic cells and boutons. Axon terminals originating in the hippocampus were labeled by acute anterograde axon degeneration induced by fimbria-fornix transection 36 hours before sacrifice. Three types of experiments were performed. The convergent catecholaminergic and hippocamposeptal innervation of LSA somatospiny neurons was studied by combining immunostaining for tyrosine hydroxylase (TH) with fimbria-fornix transection. GABAergic neurons and their hippocamposeptal afferents were identified and characterized in colchicine pretreated animals immunostained for glutamic acid decarboxylase (GAD) combined with fimbria-fornix transection. The third experiment aimed at simultaneously visualizing the relationships between catecholaminergic boutons, hippocamposeptal excitatory amino acid containing axon terminals and GABAergic profiles by double immunostaining for TH (the PAP technique) and GAD (the immunogold method) combined with fimbria-fornix transection. The results are summarized as follows: 1) The same LSA somatospiny neurons receive synaptic inputs from the hippocampus and TH immunoreactive fibers which form pericellular baskets around these cells. 2) LSA somatospiny neurons are GABAergic and are postsynaptic targets of GABAergic boutons with unknown origin and hippocamposeptal axon terminals. 3) The double immunostaining experiment, finally, provided direct evidence that the same GABAergic somatospiny neurons are postsynaptic targets of both catecholaminergic and hippocamposeptal afferents. The synaptic interconnections described in this study provide anatomical basis for a better understanding of the action of catecholamines, excitatory amino acids, and GABA on the activity of LSA neurons.

Somatospiny neurons in the rat lateral septal area are synaptic targets of hippocamposeptal fibers: A combined EM/Golgi and degejeration study

The mediolateral part of the lateral septal area (LSA) is a common target of hippocamposeptal afferents, neuropeptide containing, catecholaminergic, cholinergic, and GABAergic pericellular baskets of different origins. This specific innervation pattern as well as electrophysiological data concerning this area suggest a convergent input from different sources to particular LSA neuron populations. Light and electron microscopy combined with Golgi impregnation and acute anterograde degeneration techniques following transection of the fimbria-fornix were employed to determine whether LSA neurons with hippocampal input have any characteristic and distinctive morphological signs. About 20% of all Golgi impregnated LSA neurons were found to have somatic spines. All of these somatospiny neurons are synaptic targets of hippocamposeptal fibers. The degenerated hippocamposeptal boutons establish asymmetric synaptic contacts on their soma, somatic and dendritic spines, and on dendritic shafts. Somatospiny neurons located in the most medial and dorsal parts of the LSA seem to project toward the medial septum while all of the others appear to send descending fibers to ventral areas. Somatospiny neuron axons occasionally give out recurrent collaterals. Quantitative analysis on the spatial distribution of the somatospiny neurons revealed that practically all of them are encountered in the mediolateral division of the LSA. This area includes the lateral part of the intermediolateral septal nucleus and adjacent lateral portions of the dorsolateral and the ventrolateral septal nuclei.

Organization of the septal region in the rat brain: cholinergic-GABAergic interconnections and the termination of hippocampo-septal fibers.

This study deals with two characteristic cell types in the rat septal complex i.e., cholinergic and GABAergic neurons, and their synaptic connections. Cholinergic elements were labeled with a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme. Antiserum against glutamate decarboxylase (GAD), the GABA synthesizing enzyme, was employed to identify GABAergic perikarya and terminals, by using either the peroxidase-antiperoxidase (PAP) technique or a biotinylated second antiserum and avidinated gold or ferritin. With these contrasting immunolabels we have studied the cholinergic-GABAergic interconnections in double-labeled sections of intact septal regions and the GABAergic innervation of medial septal area cholinergic neurons in sections taken from animals 1 week following lateral septal area lesion. In other electron microscopic experiments we have studied cholinergic and GABAergic neurons in the septal complex for synaptic contacts with hippocamposeptal fibers, which were identified by anterograde degeneration following fimbria-fornix transection. Our results are summarized as follows: (1) GAD-positive terminals form synaptic contacts on ChAT-immunoreactive dendrites in the medial septum/diagonal band complex (MSDB), (2) surgical lesion of the lateral septal area resulted in a dramatic decrease of the number of GABAergic boutons on MSDB cholinergic neurons, (3) cholinergic terminals establish synaptic contacts with GAD immunoreactive cell bodies and proximal dendrites in the MSDB as well as in the lateral septum (LS), (4) degenerated terminals of hippocampo-septal fibers were mainly observed in the LS, where they formed asymmetric synaptic contacts on dendrites of GABAergic neurons and on nonimmunoreactive spines. We did not observe degenerated boutons in contact with ChAT-positive dendrites or cell bodies in the MSDB. From these results and from data in the literature we conclude that excitatory hippocampo-septal fibers activate GABAergic cells, and as yet unidentified spiny neurons in the LS, which may control the discharge of medial septal cholinergic neurons known to project back to the hippocampal formation.

Unit activity in the medial septum during differential appetitive conditioning

Unit activity in the medial septal area of the rat was studied during pavlovian appetitive differential conditioning. The firing pattern of cells in the medial septum is that of suppression to presentation of the conditioned excitor and no significant increase to the presentation of the conditioned inhibitor. This pattern is discussed in the context of a comparison with the pattern found in the lateral septal area and assesses the significance of the motivational value of the stimuli.

Localization of luteinizing hormone-releasing hormone in the forebrain of the pig.

The distribution of luteinizing hormone-releasing hormone (LHRH)-immunostained perikarya and processes was examined in the forebrains of six sexually mature female pigs by use of indirect biotin-avidin horseradish peroxidase immunocytochemistry. Two primary antisera (Drs. Y.F. Chen and V.D. Ramirez CRR11B73 and Miles-Yeda UZ-4) yielded positive staining. Adjacent sections treated either primary antiserum preabsorbed with LHRH or with normal rabbit serum substituted for primary antiserum lacked positive staining. The greatest proportion of LHRH-immunostained perikarya were found in the medial preoptic area adjacent to the organum vasculosum of the lamina terminalis. The LHRH-immunostained perikarya were also scattered rostrally in the diagonal band of Broca, and within the lateral hypothalamic area, paraventricular nucleus, periventricular zone, suprachiasmatic nucleus, and medial basal hypothalamus. LHRH-immunostained processes, which extended from the medial preoptic area, coursed either along the ventral surface to the median eminence or medially and ventrally along the third ventricular wall ventrally to the median eminence and caudally to the level of the mammillary bodies. Extrahypothalamic processes were located adjacent to the lateral ventricular floor and the third ventricle from the lateral septal area (stria terminalis) to the level of the habenular nucleus. LHRH-immunostained neurons were unipolar, bipolar, and multipolar. Close associations between individual LHRH-immunostained neurons were observed.

Distribution, morphology and habenular projections of adenosine deaminase-containing neurons in the septal area of rat

Adenosine deaminase (ADA) was localized within several types of neurons within the septum and in septal efferent projections to the habenula by immunohistochemical, biochemical, retrograde tracing and lesion methods. Numerous ADA-immunoreactive (ADA-IR) neurons were observed in the septofimbrial nucleus, the triangular septal nucleus and the bed nucleus of the anterior commissure, while considerably fewer numbers were seen in the lateral septal area. Based on their size, shape and dendritic features, 4 morphologically distinct types of ADA-IR neurons were recognized in these septal structures. In addition, fine, non-varicose, ADA-IR fibers appeared to emanate from the postcommissural cell groups and these coalesced within the stria medullaris, continued caudally within this fiber bundle, and gave rise to a dense field of very fine immunoreactive elements within a restricted zone of the dorsal half of the medial habenula. Comparisons of the habenular localization of ADA-IR and enkephalin-IR elements showed that fibers labelled for either ADA or enkephalin occupied distinct, non-overlapping regions within the dorsal half of the medial habenula. After injections of Fluoro-gold (FG) into the medial habenula, the majority of ADA-IR neurons in the septofimbrial nucleus, triangular septal nucleus, and the bed nucleus of the anterior commissure were retrogradely labelled with this fluorescent tracer, whereas no ADA-positive FG-labelled neurons were observed in the lateral septal region. Unilateral transections of the stria medullaris caused substantial depletions of ADA-immunoreactivity and reduced enzymatically determined ADA activity by up to 80% in the medial habenula on the lesioned compared with the contralateral control side. These results demonstrate that ADA-IR neurons in the septum are heterogeneously distributed and that populations of positive neurons within the postcommissural septal nuclei give rise to dense, focal projections to the medial habenula. These projections appear to be restricted to a portion of the medial habenula known to contain substance P-IR neurons and are subregionally segregated from enkephalin-positive septohabenular projections ending within this same portion. In addition to pointing out a unique capacity for adenosine catabolism within some septal neurons, possibly related to purinergic neuromodulation, the results indicate the utility of ADA-immunohistochemistry for the delineation of anatomical relationships between the septum and the medial habenula.

The effects of lesions in the lateral septal and hippocampal areas on the humoral immune response of adult female rats

There are interactions between the immune and the endocrine systems. A major role for adrenal steroids in the modulation of the immune system is well documented and the immune system can apparently activate the adrenal axis at the hypothalamic and/or pituitary level. Sex steroids modify immune function and sex differences in immune function suggest that there are also major interactions between the reproductive system and the immune system. To the extent that the endocrine system is integrated with the immune system, many of the brain areas and neural mechanisms implicated in psychoneuroendocrine processes may be involved in the regulation of psychoneuroimmune processes. We have proposed that the septal region represents an important extrahypothalamic brain area involved in modulating a variety of psychoneuroendocrine processes and now propose that the septal region may also represent an important component in the central regulation of psychoneuroimmune processes. We have tested the effects of electrolytic and kainic acid (KA) lesions in the lateral septal area of female rats and have compared the effects of KA lesions in the lateral septal area with KA lesions in the hippocampal region on antibody production following immunization with 100 μg ovalbumin in complete Freund's adjuvant. Blood samples were collected on Days 0, 7, 14, 17, and 28 following immunization in the first experiment and on Days 0, 7, 14, and 28 in the second study. All animals were injected again with ovalbumin on Day 14. The IgG, IgA, and IgM antibody titers were then measured by an enzyme-amplified ELISA assay. KA lesions in the lateral septal area produced extensive cell loss in this region and produced a concurrent loss of cell bodies in the CA 3-CA 4 hippocampal areas. Compared to sham and electrolytic septal lesioned rats, KA lesions of the lateral septal area significantly reduced IgG titers on Days 7 and 17 with a trend for Day 14. Similarly, the IgA and IgM titers were significantly lower on Days 7, 14, and 17 for the rats with KA lesions in the lateral septal area. In addition, the KA septal lesioned rats gained more body weight and had higher thymus weights, relative to the electrolytic lesioned and sham groups. In addition, the rats with KA lesions in the hippocampal area showed significantly higher IgM titers on Day 7, elevated IgG titers on Day 14, and lower IgA titers on Day 28, relative to the sham group. When the rats were reimmunized with a new antigen, β-lactoglobulin, the inhibitory and facilitory effects of septal and hippocampal lesions on antibody production, respectively, were still present, suggesting that these effects are sustained. The decrease in immune response of rats with KA lesions in the lateral septal area cannot be accounted for by the concurrent hippocampal damage typically associated with these neurotoxic lesions, since the effects of lesions restricted to the hippocampus were generally opposite to those of KA lesions in the septal area. These results suggest that neuroendocrine and neuroimmune regulatory processes are modulated by a common control system and the septal-hippocampal complex appears to be an important component in this control system.

Female sexual behavior in the golden hamster following kainic acid lesions in the lateral septal area

Patterns of female sexual behavior in the hamster are qualitatively different from that observed in the rat. Hamsters demonstrate tonic immobility and a sustained lordotic response that can last for several minutes following minimal stimulation from the male while in rats, the lordotic response is highly depedent upon continued stimulation from the male and lasts for only a few seconds following a mount or intromission. Also, the hamster requires both estrogen and progesterone priming in order to display female sexual behavior but the rat can show lordotic behavior following treatment with estrogen alone. Electrolytic lesions in the lateral septal area of female rats produce a facilitation in female sexual behavior and increase behavioral sensitivity to estrogen. However, lesions in the lateral septal area of rats produced by the neurotoxin kainic acid (KA) result in deficits in female sexual behavior following estrogen and progesterone treatment. Given these species differences in sexual behavior, we have examined the effects of KA lesions in the lateral septal area of hamsters on female sexual behavior. Adult female golden hamsters were ovariectomized and tested for female sexual behavior prior to receiving brain surgery. For all behavior tests, animals were injected SC with 60 μg of estradiol benzoate/kg per day for two days and 0.5 mg of progesterone three hours prior to the behavior test on day three. Behavior tests consisted of placing the test animal in a male's home cage for 10 minutes and recording the latency to the first lordosis, length of the longest single bout of lordosis and total lordosis duration. Either KA (0.375 μg in 0.5 μl) or saline (control) were infused bilaterally into the lateral septal area. All animals were tested again for female sexual behavior at one and three weeks following brain surgery. There were no differences between the lesion and control groups for the pre-lesion behavior tests and the performance of the sham operated animals was comparable between the post- vs. pre-lesion tests. However, following brain surgery, the KA lesioned animals were significantly different from the sham operated controls on all behavioral measures. The KA lesioned animals showed significantly longer latencies to the first lordosis, significantly shorter single bouts of lordosis and significantly shorter total duration of lordosis for both behavior tests, relative to the controls. Thus, despite the large species differences in the display of female sexual behavior between rats and hamsters, KA lesions of the lateral septal area produce a similar deficit in female lordotic behavior. Thus, in addition to the known inhibitory role of the septal region, this brain area also exerts facilitatory control on female sexual behavior in both rats and hamsters.

The differential ascending projections from the anterior, central and posterior regions of the lateral hypothalamic area: An autoradiographic study

The ascending efferent projections of the neurons of the anterior (LHAa), central (LHAc) and posterior (LHAp) parts of the lateral hypothalamic area (LHA) have been studied using an autoradiographic analysis of the anterograde axonal transport after local injection of tritiated amino acids. Our results show that LHA regions have common projections particularly to the thalamus and to the hypothalamus. They also demonstrate the existence of differential projections: i.e. an anteroposterior gradient of projection sites according to anterior, central and posterior localisation of the LHA neurons. The LHAa neuronal projections terminate in the lateral septal area; the LHAc projections innervate the frontal cortex while LHAp neurons send their projections to the olfactory bulb and innervate both the cerebral cortex and the hippocampus. Only the LHAp neurons project measurably to the globus pallidus, the caudate putamen and the nucleus accumbens.

Serotonin mediates cardiovascular responses to acetylcholine, bradykinin, angiotensin II and norepinephrine in the lateral septal area of the rat brain

The infusion of acetylcholine, bradykinin, angiotensin II, norepinephrine and serotonin into the lateral septal area produced a dose-dependent increase of arterial blood pressure and heart rate. A pattern of inhibition of these cardiovascular responses, produced by pretreatment of the lateral septal area with phentolamine, 6-hydroxydopamine, methysergide and 5,7-dihydroxytryptamine was disclosed. These results suggest that the effects of acetylcholine, bradykinin and partially of angiotensin II, depend on the release of norepinephrine and the actions of this neurotransmitter in turn depend on the integrity of the serotonergic system in the lateral septal area.

Quantitative autoradiographic maps of local cerebral glucose metabolism in awake rats: I. Septal region and anterior hypothalamus.

Quantitative 14C-2-deoxyglucose autoradiography was used to determine the local cerebral glucose metabolic rate (lCMRG) of nuclei in the septal region and anterior hypothalamus of awake, unanesthetized rats. The lCMRG of the medial and lateral septal areas, preoptic areas, medial preoptic nuclei, suprachiasmatic nuclei, supraoptic nuclei, anterior hypothalamic nuclei, and paraventricular nuclei were measured. The lCMRG of each nucleus was mapped at successive rostral-caudal levels to determine significant internuclear and intranuclear variations. These data provide a detailed neuroanatomic map of cerebral energy metabolism of the septal and anterior hypothalamic regions in animals under standardized conditions.

Muscarinic ml receptors in the lateral septal area mediate cardiovascular responses to cholinergic agonists and bradykinin: supersensitivity induced by chronic treatment with atropine

The infusion of pilocarpine, acetylcholine, bradykinin and the selective Ml muscarinic agonist McNeil-A-343 into the lateral septal area produced a dose-dependent increase of arterial blood pressure and heart rate. The M2 muscarinic agonist carbamylcholine that causes a rise in arterial blood pressure when injected into the anterior lateral ventricles did not produce any cardiovascular effects when infused into the lateral septal area. Chronic treatment with atropine induced supersensitivity to the muscarinic agonists and a significant increase in the number of muscarinic receptors. In this study bradykinin failed to produce any significant change in cardiovascular activity. Pirenzepine, a M1 muscarinic blocking agent, inhibited completely the effect of both muscarinic agonists and bradykinin on cardiovascular activity. In fact, in vitro studies shows that the displacement of the binding of [ 3H]QNB by pirenzepine is compatible with the presence of the M1 subtype of muscarinic receptor in the lateral septal area, where it may play a major role on cardiovascular regulation.

Interaction between acetylcholine and bradykinin in the lateral septal area of the rat brain: Involvement of muscarinic receptors in cardiovascular responses

The lateral septal area was used as a model to study the interaction between acetylcholine (Ach) and bradykinin on arterial blood pressure, since both mediators are present in this region. In the lateral septal area, the administration of the peptide or Ach produced a long-lasting, sympathetic-mediated increase of arterial blood pressure which was blocked by atropine. Pretreatment of the lateral septal area with hemicholinium-3, which depletes stores of acetylcholine, partially blocked the pressor effect of bradykinin but not that of Ach. Captopril—an inhibitor of kininase II—enhanced the pressor effects of bradykinin and Ach. Synaptosomal studies showed that bradykinin increased sodium-dependent, high-affinity uptake of choline and the conversion of [ 3H]choline to [ 3H]acetylcholine. Competition experiments using the highly specific muscarinic antagonist [ 3H]quinuclidinyl benzilate, demonstrated that bradykinin displaced the muscarinic antagonist from its receptor-ligand complexes. These results suggest that in the lateral septal area acetylcholine and bradykinin interact in a positive feed-back which amplifies pressor responses.

Central adrenergic mediation of the cardiovascular effect of intraventricular bradykinin.

The lateral septal area of anaesthetized rats was perfused using a push-pull cannula and the effect of the intracerebroventricular injection of bradykinin on the release of 3H-noradrenaline from the lateral septal area studied. A significant increase in 3H-noradrenaline release concomitant to a cardiovascular response was observed after bradykinin administration, suggesting the involvement of septal noradrenergic mechanisms in the response to the peptide. Morphine, subcutaneously administered, blocked the increase in the effluent radioactivity and the cardiovascular response to bradykinin, suggesting that the bradykinin receptors in the septal area are similar to those found in the sympathetic ganglia. Intravenous injection of diphenhydramine blocked the cardiovascular response to bradykinin but not the 3H-noradrenaline release, indicating the involvement of histaminergic mechanism in a step posterior to the release of catecholamines in the septal area.

Intraseptal microinjections of carbachol and angiotensin II in rats: Effects on taste preferences

The present study examined the effects of carbachol and angiotensin II injected into the medial and lateral septal areas (MSA and LSA) on the ingestion of primary taste solutions in a free-choice situation. The injection of carbachol or angiotensin II into MSA and LSA of water sated rats evoked a preference for the sweet tasting saccharin solution and water. The lateral septal rats also preferred acetic acid solution. Only the total fluid intake differed significantly among the four groups. In the water deprived rats injection of chemical to the respective groups induced the ingestion of NaCl solution. The MSA rats on injection of carbachol also preferred saccharin apart from NaCl. There was a significant difference in the NaCl intake among the four groups. The quinine solution was not consumed by all the groups. These results indicate that both the carbachol and angiotensin II induce the ingestion of saccharin, NaCl and water. The MSA might be more sensitive in inducing NaCl intake as compared with LSA during deprivation schedule and cholinergic stimulation. The LSA also evokes a preference for the sour tasting acetic acid. Furthermore, the data also suggest that the neurons sensitive to angiotensin are more potent than cholinergic neurons of LSA in producing salt preference.

Neuroestrogenic control of feeding behavior and body weight in rats with kainic acid lesions of the lateral septal area

The role of the lateral septal area (LS) in the regulation of energy balance and the estrogenic control of feeding behavior in the female rat has been examined. Food intake (FI) and body weight (BWt) were measured daily following kainic acid (KA) LS lesions (KALS) to assess any regulatory changes in energy balance. In all animals KA lesions of the LS produced major cell loss in the LS; however the extent of damage was variable. Associated with KA lesions of the LS was the concurrent loss of CA3-CA4 cell groups in the hippocampus which was comparable for all the lesioned animals. The extent of septal damage was quantified morphometically and correlated with changes in FI and BWt following estrogen treatment. The significant effects of the KALS lesions, relative to the control animals were: (1) an increase in BWt which was statistically significant 22 days following brain surgery, (2) an increase in daily FI which was significant by day 6 post surgery, (3) an attenuation in the anorexic effects of estrogen on FI and BWt, and (4) a significant decrease in the percent days of vaginal estrus. Moreover, the anorexic effects of estrogen were significantly correlated with the extent of LS damage, but not the amount of hippocampal damage. The present study confirms that an increase in BWt is produced by KA lesions of the LS and further indicates that a sustained period of increased FI precedes the increase in BWt. Also these results verify that cells in the LS are involved in the estrogenic control of energy balance and further suggest that the increase in FI and BWt following KA lesions of the LS is attributable to the concurrent reduction in the anorexic effects of estrogen. The morphometic analysis of the brain lesions further suggest the ventral and/or intermediate subdivisions of the LS as the location of the cell bodies that modulate the estrogenic control of feeding behavior.

The effects of unilateral frontolateral hypothalamic knife cuts and asymmetrical unilateral septal lesions on lordosis behavior of rats

It has been shown that the medial hypothalamus exerts facilitatory control over female sexual behavior in the rat whereas the septal area exerts inhibitory control over lordosis behavior. The present study assessed whether the septal area exerts its inhibitory control over lordosis behavior via efferent connections with the mediobasal hypothalamus. Anatomical studies using retrograde tracers verified that cell bodies located in the lateral septal area project ipsilaterally to the mediobasal hypothalamus. Based upon the predominantly ipsilateral connection between the lateral septum and mediobasal hypothalamus, unilateral frontolateral knife cuts were produced on the left or right side of the mediobasal hypothalamus or else sham surgeries. Subsequently all animals were given unilateral electrolytic septal lesions on the right side of the brain. These animals had septal damage that was located either ipsilateral or contralateral with respect to the knife cuts. Female sexual behavior was tested following the hypothalamic knife cuts and retested after unilateral septal lesions. Unilateral hypothalamic knife cuts on either side of the brain had no detectable effect on female sexual behavior when compared to the sham group. However, following unilateral septal lesions a significant increase in lordosis behavior was observed in all groups following treatment with estrogen alone. There were no differences in lordosis behavior between the groups which had septal lesions located ipsilateral vs. contralateral with respect to the hypothalamic knife cuts. These results support the hypothesis that the facilitation in lordosis behavior associated with electrolytic septal lesions is not mediated by neural connections between the septal area and mediobasal hypothalamus. These two brain areas thus appear to exert separate and independent control over female sexual behavior.

The calcitonin gene-related peptide-containing fiber projection from the hypothalamus to the lateral septal area including its fine structures

The afferent source of calcitonin gene-related peptide-like immunoreactive (CGRPI) fibers in the lateral septal area of the rat was sought by using indirect immunofluorescence technique. These fibers decreased markedly on the operated side after the destruction of the area between the anterior hypothalamic nucleus and the lateral hypothalamus where a number of CGRPI cells. We also examined the fine structure of CGRPI fibers in the lateral septal area. Many CGRPI fibers forming axosomatic synapses were identified. These facts strongly suggest that CGRPI cells in the area between the anterior hypothalamic nucleus and the lateral hypothalamus project ipsilaterally to the lateral septal area and directly influence the soma there.

Thirst and vasopressin secretion following central administration of angiotensin II in rats with lesions of the septal area and subfornical organ

Various dipsogenic stimuli, including peripheral and central administration of angiotensin II, have been shown to be capable of releasing vasopressin from the neurohypophyseal system. Studies were carried out in the rat to investigate whether the septal area, which contains a high concentration of angiotensin-sensitive cells and has neural connections with hypothalamic vasopressin-secreting neurons, mediated the stimulatory effect produced by angiotensin II on vasopressin release. Rats with electrolytic lesions in the region of the septal area had increased daily water consumption and urine output when these lesions included the medioventral or lateral nuclei of the septal forebrain, but not when the lesion involved the subfornical organ. No difference was observed in drinking responses following water deprivation or intracerebroventricular injection of angiotensin II in all experimental groups. In addition, the impaired ability to maintain water homeostasis (polyuro-polydipsic syndrome) of septal-lesioned rats was associated with decreased levels of circulating radioimmunoassayable vasopressin. Furthermore, the vasopressin release which occurred in response to intracerebroventricular angiotensin II in normal controls, shamlesioned and subfornical organ-lesioned rats was significantly attenuated in rats with electrolytic lesion of the medioventral or lateral septal area. Since cells in the lateral septal area are excited by iontophoretic application of angiotensin II, the present data might be consistent with the hypothesis that the stimulatory effect produced by central administration of angiotensin II on vasopressin release rests upon the integrity of the lateral septal area.