Gonadal Hormone-Dependent Sexual Differentiation of a Female-Biased Sexually Dimorphic Cell Group in the Principal Nucleus of the Bed Nucleus of the Stria Terminalis in Mice.

We recently reported a female-biased sexually dimorphic area in the mouse brain in the boundary region between the preoptic area and the bed nucleus of the stria terminalis (BNST). We reexamined this area and found that it is a ventral part of the principal nucleus of the BNST (BNSTp). The BNSTp is a male-biased sexually dimorphic nucleus, but the ventral part of the BNSTp (BNSTpv) exhibits female-biased sex differences in volume and neuron number. The volume and neuron number of the BNSTpv were increased in males by neonatal orchiectomy and decreased in females by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth. Sex differences in the volume and neuron number of the BNSTpv emerged before puberty. These sex differences became prominent in adulthood with increasing volume in females and loss of neurons in males during the pubertal/adolescent period. Prepubertal orchiectomy did not affect the BNSTpv, although prepubertal ovariectomy reduced the volume increase and induced loss of neurons in the female BNSTpv. In contrast, the volume and neuron number of male-biased sexually dimorphic nuclei that are composed of mainly calbindin neurons and are located in the preoptic area and BNST were decreased by prepubertal orchiectomy but not affected by prepubertal ovariectomy. Testicular testosterone during the postnatal period may defeminize the BNSTpv via binding directly to the androgen receptor and indirectly to the estrogen receptor after aromatization, although defeminization may proceed independently of testicular hormones in the pubertal/adolescent period. Ovarian hormones may act to feminize the BNSTpv during the pubertal/adolescent period.

Effect of inhibition of the central nucleus of the amygdala and drug experience on the regions underlying footshock-induced reinstatement of morphine seeking.

This study assessed the effect of inhibition of the central nucleus of the amygdala (CeA) and drug experience on brain regions underlying footshock-induced reinstatement of morphine-seeking behaviour in rats. The difference in time spent in two chambers of a place preference apparatus was used to measure morphine-conditioned place preference. Fos was measured as a marker of neuronal activation in the ventral bed nucleus of the stria terminalis (BNSTv) and ventral tegmental area (VTA). Footshock was found to enhance Fos expression in the BNSTv regardless of drug experience. In the VTA, morphine and footshock had an interactive effect on the increase in Fos expression. Inhibition of the CeA decreased Fos expression in the BNSTv regardless of drug experience, whereas in the VTA this effect only occurred in morphine-treated rats. These results suggest that drug experience has no differential effect on the BNSTv however morphine produces footshock sensitization in the VTA. CeA inhibition modulates the footshock-induced activity of these regions of the brain and attenuates reinstatement of drug seeking behaviour.

Effects of sexual experience on conspecific odor preference and male odor-induced activation of the vomeronasal projection pathway and the nucleus accumbens in female rats.

In the present study in estrogen-progesterone primed ovariectomized female rats, we examined the expression of a preference for male odors and male odor-induced Fos immunoreactivity throughout the vomeronasal projection pathway and the nucleus accumbens (NAcc), using both sexually experienced and sexually naive subjects. Female rats significantly preferred airborne odors and soiled bedding from sexually active males over those from estrous females, irrespective of the presence or absence of prior sexual experience. On the other hand, the brain regions in which exposure to male-soiled bedding significantly increased Fos expression were different between sexually experienced and sexually naive subjects. Significant increment of Fos expression in the posterior-dorsal medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in forebrain, as well as the accessory olfactory bulb, was observed in both groups of subjects. Fos expression in the anterior-dorsal medial amygdala (MeAD), the medial preoptic area (mPOA) and the NAcc core, however, was significantly increased only in the sexually experienced subjects. These results suggested that male odor-induced activations of the MePD and/or the BNST, but not of the MeAD, the mPOA and the NAcc core, are required for the expression of a male-directed odor preference in female rats.

Differential c-fos expression in the brain of male Japanese quail following exposure to stimuli that predict or do not predict the arrival of a female.

We investigated the effects of presenting a sexual conditioned stimulus on the expression of c-fos in male Japanese quail. Eight brain sites were selected for analysis based on previous reports of c-fos expression in these areas correlated with sexual behaviour or learning. Males received either paired or explicitly unpaired presentations of an arbitrary stimulus and visual access to a female. Nine conditioning trials were conducted, one per day, for each subject. On the day following the ninth trial, subjects were exposed to the conditional stimulus (CS) for 5 min. Conditioning was confirmed by analysis of rhythmic cloacal sphincter movements (RCSM), an appetitive sexual behaviour, made in response to the CS presentation. Subjects in the paired condition performed significantly more RCSM than subjects in the unpaired group. Brains were collected 90 min following the stimulus exposure and stained by immunohistochemistry for the FOS protein. Significant group differences in the number of FOS-immunoreactive (FOS-ir) cells were found in two brain regions, the nucleus taeniae of the amygdala (TnA) and the hippocampus (Hp). Subjects in the paired condition had fewer FOS-ir cells in both areas than subjects in the unpaired condition. These data provide additional support to the hypothesis that TnA is implicated in the expression of appetitive sexual behaviours in male quail and corroborate numerous previous reports of the involvement of the hippocampus in conditioning. Further, these data suggest that conditioned and unconditioned sexual stimuli activate different brain regions but have similar behavioural consequences.

Altered maternal profiles in corticotropin-releasing factor receptor 1 deficient mice.

BACKGROUND: During lactation, the CNS is less responsive to the anxiogenic neuropeptide, corticotropin-releasing factor (CRF). Further, central injections of CRF inhibit maternal aggression and some maternal behaviors, suggesting decreased CRF neurotransmission during lactation supports maternal behaviors. In this study, we examined the maternal profile of mice missing the CRF receptor 1 (CRFR1). Offspring of knockout (CRFR1-/-) mice were heterozygote to offset possible deleterious effects of low maternal glucocorticoids on pup survival and all mice contained a mixed 50:50 inbred/outbred background to improve overall maternal profiles and fecundity. RESULTS: Relative to littermate wild-type (WT) controls, CRFR1-/- mice exhibited significant deficits in total time nursing, including high arched-back, on each test day. Consistent with decreased nursing, pups of CRFR1-deficient dams weighed significantly less than WT offspring. Licking and grooming of pups was significantly higher in WT mice on postpartum Day 2 and when both test days were averaged, but not on Day 3. Time off nest was higher for CRFR1-/- mice on Day 2, but not on Day 3 or when test days were averaged. Licking and grooming of pups did not differ on Day 2 when this measure was examined as a proportion of time on nest. CRFR1-/- mice showed significantly higher nest building on Day 3 and when tests were averaged. Mean pup number was almost identical between groups and no pup mortality occurred. Maternal aggression was consistently lower in CRFR1-/- mice and in some measures these differences approached, but did not reach significance. Because of high variance, general aggression results are viewed as preliminary. In terms of sites of attacks on intruders, CRFR1-/- mice exhibited significantly fewer attacks to the belly of the intruder on Day 5 and when tests were averaged. Performance on the elevated plus maze was similar between genotypes. Egr-1 expression differences in medial preoptic nucleus and c-Fos expression differences in bed nucleus of stria terminalis between genotype suggest possible sites where loss of gene alters behavioral output. CONCLUSION: Taken together, the results suggest that the presence of an intact CRFR1 receptor supports some aspects of nurturing behavior.

Reproductive aging in Japanese quail, Coturnix japonica is associated with changes in central opioid receptors.

Quantitative in vitro autoradiography was used to measure specific mu and delta opioid receptor densities in regions of the Japanese quail, Coturnix japonica, brain that regulates reproductive endocrine and behavioral responses to determine the possible involvement of the opioid system in reproductive decline seen during aging. Densities were measured in selected brain regions of young sexually active (YAM), young photoregressed (YPM), old reproductively senescent (OIM) male, young active (YF), and old senescent female (OF) Japanese quail. Medial and lateral septum (SM, SL), medial preoptic area (POM), and n. intercollicularis (ICo) were of particular interest for reproductive responses. Similar to previous observations, mu and delta opioid receptors showed differential distributions in the areas measured. Some age-related changes were observed, with lower SM mu receptor densities in aged males (OIM) than females or young males (YAM). Densities of mu receptors in the POM and in other areas examined did not vary with sex or age. Similarly, OIM males had lower densities of delta receptors in the SM than young males (YAM and YPM); POM delta receptor densities were also low in OIM males compared to the YPM males, and YAM males were intermediate. Interestingly, photoregressed males (YPM) had higher SL delta receptor densities than any other group. Thus there were age-related differences detected in mu receptor densities among groups in the SM of OIM relative to other groups; and the mu and delta receptor densities did not differ in females with brain region. Additionally for delta receptors specifically, YF and OF did not differ from OIM for any brain region and similarly had lower densities of delta receptors compared to YAM males. These data provide support for regional differences in opioid receptor distribution and for age- and sex-related differences in delta opioid receptor densities. The direction of change presents an interesting dichotomy in that, compared to young active males, delta opioid receptor densities increased with loss of reproductive function in the YPM, whereas receptor densities decreased in the OIM. Plasma androgen levels were relatively low in both these groups compared to the young active males. This observation suggests that there is an age-related loss in the ability of this receptor system to respond to circulating and centrally produced steroid hormones in the POM and in some septal regions, compared to young animals that are responding to environmental cues. Furthermore, these data support an active role of the opioid peptide system in the inhibition of the reproductive axis in photoregression.

Conditional CRF receptor 1 knockout mice show altered neuronal activation pattern to mild anxiogenic challenge.

RATIONALE: Regional-specific corticotropin-releasing factor receptor 1 (CRF-R1) knockout mice have been generated recently as a tool to dissociate CNS functions modulated by this receptor. In these mice, CRF-R1 function is postnatally inactivated in the anterior forebrain including limbic brain structures but not in the pituitary leading to normal activity of the hypothalamic-pituitary-adrenocortical (HPA) axis under basal conditions and reduced anxiety-related behavior in the light-dark box and the elevated plus maze (EPM) as compared to wild-type (WT) mice (Müller et al., Nat Neurosci 6:1100-1107, 2003). OBJECTIVE: To identify neurobiological correlates underlying this reduced anxiety-like behavior, the expression of c-Fos, an established marker for neuronal activation, which was examined in response to a mild anxiogenic challenge. MATERIALS AND METHODS: Mice were placed for 10 min on the open arm (OA) of the EPM, and regional c-Fos expression was investigated by immunohistochemistry. RESULTS: OA exposure enhanced c-Fos expression in both conditional CRF-R1 knockout and WT mice in a number of brain areas (39 of 55 quantified), including cortical, limbic, thalamic, hypothalamic, and hindbrain regions. The c-Fos response in conditional CRF-R1 knockout animals was reduced in a restricted subset of activated neurons (4 out of 39 regions) located in the medial amygdala, ventral lateral septum, prelimbic cortex, and dorsomedial hypothalamus. CONCLUSIONS: These results underline the importance of limbic CRF-R1 in modulating anxiety-related behavior and suggest that reduced neuronal activation in the identified limbic and hypothalamic key structures of the anxiety circuitry may mediate or contribute to the anxiolytic-like phenotype observed in mice with region-specific deletion of forebrain CRF-R1.

Steroid hormone mediation of limbic brain plasticity and aggression in free-living tree lizards, Urosaurus ornatus.

The neural mechanisms by which steroid hormones regulate aggression are unclear. Although testosterone and its metabolites are involved in both the regulation of aggression and the maintenance of neural morphology, it is unknown whether these changes are functionally related. We addressed the hypothesis that parallel changes in steroid levels and brain volumes are involved in the regulation of adult aggression. We examined the relationships between seasonal hormone changes, aggressive behavior, and the volumes of limbic brain regions in free-living male and female tree lizards (Urosaurus ornatus). The brain nuclei that we examined included the lateral septum (LS), preoptic area (POA), amygdala (AMY), and ventromedial hypothalamus (VMH). We showed that the volumes of the POA and AMY in males and the POA in females vary with season. However, reproductive state (and thus hormonal state) was incompletely predictive of these seasonal changes in males and completely unrelated to changes in females. We also detected male-biased dimorphisms in volume of the POA, AMY, and a dorsolateral subnucleus of the VMH but did not detect a dimorphism between alternate male morphological phenotypes. Finally, we showed that circulating testosterone levels were higher in males exhibiting higher frequency and intensity of aggressive display to a conspecific, though brain nucleus volumes were unrelated to behavior. Our findings fail to support our hypothesis and suggest instead that plasma testosterone level covaries with aggression level and in a limited capacity with brain nucleus volumes but that these are largely unrelated relationships.

Role of noradrenergic receptors in the bed nucleus of the stria terminalis in regulating pulsatile luteinizing hormone secretion in female rats.

The bed nucleus of the stria terminalis (BNST) is one of the brain areas densely innervated by noradrenergic neurons originating in the brain stem. The present study aims to determine the role of noradrenergic receptors in the BNST in regulating pulsatile luteinizing hormone (LH) secretion in female rats. Ovariectomized (OVX) or estrogen-primed OVX (OVX+E2) rats received three 1-h-interval injections of 0.05 micromol of noradrenaline (NA), phenylephrine (alpha1-adrenergic receptor agonist), clonidine (alpha2-agonist), or isoproterenol (beta-agonist) into the BNST. Injection of NA or alpha1-adrenergic agonist into the BNST strongly suppressed pulsatile LH secretion in OVX+E2 rats with a significant (P < 0.05) decrease in the mean LH level for 3 h and LH pulse frequency, but alpha2-and beta-agonists did not affect any of the LH pulse parameters. In OVX animals, alpha1- and alpha2-adrenergic agonists caused a significant change in LH pulse frequency and amplitude, respectively, though the effect was not as apparent as the NA- or alpha1-agonist-induced changes in OVX+E2 animals. These results indicate that NA inputs to the BNST suppress pulsatile LH secretion via alpha1-adrenergic receptors and that estrogen enhances this suppression.

Microscopic stucture of the lamina terminalis: implications for microsurgical third ventriculostomy.

OBJECTIVE: The neurosurgical approach through the lamina terminalis (LT) is a commonly used technique for management of the third ventricle region pathology. Furthermore, LT fenestration is a recommended procedure during surgery of ruptured intracranial aneurysms. Though the LT is a rudimentary structure in adult human brain, its neurosurgical significance is eliciting increasing interest. The aim of the presented study is to characterize the LT histologically, with special attention to the previously recommended area of LT fenestration and to the localization and structure of the organum vasculosum lamina terminalis (OVLT). METHODS: The study was performed on tissue sampled from eight formalin-fixed brains. Paraffin sections taken from various levels of the LT were routinely stained with hematoxylin and eosin (H&E) and by immunohistochemical methods. RESULTS: The LT in the inferior part bordering the optic recess and immediately above the optic chiasm exhibited paucicellular, mainly fibrillar, glial tissue with scanty neural elements and small vessels. At about halfway along the length of the LT an area of loose structure, with an increased number of glial cells, small neurons and thin-walled vessels corresponding to the OVLT was observed. In the majority of examined cases the OVLT was poorly developed and was therefore sometimes overlooked. The superior segment of the LT near the anterior commissure disclosed again paucicellular and slightly loosened fine fibrillar tissue. CONCLUSIONS: The results of the present microscopic study confirm the opinion that the inferior segment of the LT is the most convenient place for safe incision. Its thinnest middle part immediately above the optic recess is composed mainly of gliotic tissue. Above, prominent loosened tissue and the rather rudimental structure of the OVLT seem to be additional favorable factors for a safe fenestration of the LT.

Evidence that projections from the bed nucleus of the stria terminalis and from the lateral and medial regions of the preoptic area provide input to gonadotropin releasing hormone (GNRH) neurons in the female sheep brain.

The arcuate nucleus/ventromedial hypothalamic nucleus (ARC/VMH) region is thought to relay estrogen feedback signals to gonadotropin-releasing hormone (GnRH) cells in the sheep brain. This region sends major projections to the lateral preoptic area (lPOA), ventral bed nucleus of the stria terminals (vBnST) and the ventro-caudal division of the median preoptic nucleus (vcMePON) with little direct input to GnRH cell bodies, suggesting interneuronal relay to GnRH neurons. The brain stem also provides input to the POA. The present study aimed to identify possible relay circuits in the POA and BnST to GnRH neurons. Biotinylated dextran amine (BDA) was injected into lPOA (n=6), vBnST (n=2), vcMePON (n=3) and periventricular nucleus (PeriV; n=1) of ewes for anterograde tracing. GnRH immunoreactive (IR) perikarya appearing to receive input from BDA-containing varicosities were identified by fluorescence microscopy, with further analysis by confocal microscopy. When BDA was injected into rostral and caudal regions of lPOA (n=3), no tracer-filled varicose fibers were found in contact with GnRH-IR perikarya. Injections into the center of the lPOA (n=3) indicated direct projections to GnRH-IR cells. Injections into the vBnST, vcMePON and PeriV indicated that cells of these regions also provide input to GnRH cells. BDA-containing varicosities found in the MPOA were immunoreactive for NPY or were GABAergic or glutamatergic when the tracer was injected into vBnST and lPOA, but not when injections were placed in the vcMePON. With injection into the PeriV, tracer-filled varicosities in the MPOA were not immunoreactive for somatostatin or enkephalin. Injection of FluoroGold into ventral POA retrogradely labeled cells in the above mentioned areas, but few were also immunoreactive for estrogen receptor-alpha. Thus, cells of the vBnST, lPOA, vcMePON and PeriV project to GnRH neurons. These cells may provide an interneuronal route to GnRH neurons from the ARC/VMH, the brain stem and other regions of the brain.

Functional mapping of the prosencephalic systems involved in organizing predatory behavior in rats.

The study of the neural basis of predatory behavior has been largely neglected over the recent years. Using an ethologically based approach, we presently delineate the prosencephalic systems mobilized during predation by examining Fos immunoreactivity in rats performing insect hunting. These results were further compared with those obtained from animals killed after the early nocturnal surge of food ingestion. First, predatory behavior was associated with a distinct Fos up-regulation in the ventrolateral caudoputamen at intermediate rostro-caudal levels, suggesting a possible candidate to organize the stereotyped sequence of actions seen during insect hunting. Insect predation also presented conspicuous mobilization of a neural network formed by a distinct amygdalar circuit (i.e. the postpiriform-transition area, the anterior part of cortical nucleus, anterior part of basomedial nucleus, posterior part of basolateral nucleus, and medial part of central nucleus) and affiliated sites in the bed nuclei of the stria terminalis (i.e. the rhomboid nucleus) and in the hypothalamus (i.e. the parasubthalamic nucleus). Accordingly, this network is likely to encode prey-related motivational values, such as prey's odor and taste, and to influence autonomic and motor control accompanying predatory eating. Notably, regular food intake was also associated with a relatively weak Fos up-regulation in this network. However, during regular surge of food intake, we observed a much larger mobilization in hypothalamic sites related to the homeostatic control of eating, namely, the arcuate nucleus and autonomic parts of the paraventricular nucleus. Overall, the present findings suggest potential neural systems involved in integrating prey-related motivational values and in organizing the stereotyped sequences of action seen during predation. Moreover, the comparison with regular food intake contrasts putative neural mechanisms controlling predatory related eating vs. regular food intake.

In vivo gene transfer to the brain cortex using a single injection of HSV-1 vector into the medial septum.

This study shows that an ICP4-replication-deficient herpes simplex virus containing the Moloney murine leukaemia virus LTR fused with the coding sequence for the beta-galactosidase gene can be used as a very effective vector for delivering the beta-galactosidase reporter gene into the rat brain septum. F344 rats received bilateral stereotaxic injections into the nucleus of the diagonal band and into the medial septum. The X-gal stain was used to detect the activity of the expressed beta-galactosidase enzyme. The delivered reporter gene was expressed successfully not only in the neuronal cells of the injected areas but also in cells that project to the injection area such as cortex cells about 6 mm away from the injection sites. Expression was visible at 1, 3 and 9 weeks following injection. We conclude that this vector can effectively deliver genes into different regions of the mature mammalian brain and also to areas distant from the injection site.

Release of oxytocin in the hypothalamic paraventricular nucleus, but not central amygdala or lateral septum in lactating residents and virgin intruders during maternal defence.

In lactating rats, the neuroendocrine responses of the oxytocinergic system and the hypothalamo-pituitary-adrenal axis to various kinds of stressors are attenuated. In this study, using intracerebral microdialysis in combination with a highly sensitive radioimmunoassay, we characterised oxytocin (OXT) release within the paraventricular nucleus (PVN), the central amygdala (CeA), and the medio-lateral septum (mS) before, during and after a psycho-social stressor (the maternal defence test) in both the virgin intruder and the lactating resident rat (day 3 of lactation). Within the PVN, local OXT release was found to increase significantly in virgin intruders during exposure to the resident (2.1-fold, P < 0.05), as well as in lactating residents when exposed to the virgin intruder, though to a lesser extent when compared with basal levels (1.7-fold, P < 0.05). In contrast, OXT release remained unchanged within the CeA and the mS of both virgin intruders and lactating residents. Release of OXT under basal conditions was clearly above the detection limit of the radioimmunoassay, and did not differ between lactating and virgin rats in any of the brain regions studied. Our study also demonstrates that recent surgery or ongoing intracerebral microdialysis does not affect the behavioural performance of the intruders or residents when comparing dialysed and non-dialysed rats. The results indicate that exposure to the maternal defence test is a relevant stressor for the brain OXT system which becomes activated in both intruder and resident rats, although to varying degrees depending upon their reproductive status and in a region-dependent manner. The behavioural and/or neuroendocrine functions of intra-PVN released OXT during this psycho-social challenge remain to be clarified.

Immunocytochemical evidence for the striatal nature of the rat lateral part of interstitial nucleus of the posterior limb of the anterior commissure (IPAC).

The present study focuses on the basal forebrain region originally designated as fundus striati, but currently known as 'interstitial nucleus of the posterior limb of the anterior commissure' (IPAC). Using multiple immunofluorescence of the calcium-binding proteins parvalbumin and calbindin, the GABA(A) receptor alpha1-subunit, vasoactive intestinal polypeptide (VIP), met(5)-enkephalin (MENK) and glutamic acid decarboxylase (GAD), it was shown that VIP-immunostained axons, which are typical for major parts of the extended amygdala, densely innervate only the medial part of IPAC, while they are absent in the lateral part. On the other hand, large-sized GABAergic, parvalbumin- and GABA(A) receptor alpha1-subunit-immunoreactive neurons, which are densely covered by separate GAD- and MENK-immuno reactive terminals and a type of medium-sized alpha1-subunit-monolabelled cells, occur in the dorsal striatum and in the adjacent lateral part of IPAC as well. Large-sized neurons double labelled for parvalbumin and the GABA(A) receptor alpha1-subunit are also widely distributed in the neighbouring ventral pallidum. Neurons of this type are absent, however, in the medial part of IPAC and other extended amygdala subunits. Our findings confirm the recent suggestion of a morphofunctional dichotomy of IPAC (Comp. Neurol. 439 (2001) 104), as only the medial part reveals characteristics as typical for extended amygdala, while its lateral part exhibits cytochemical peculiarities of striatal tissue. Therefore, the term 'lateral part of IPAC' should be replaced by the term 'putaminal fundus (fundus putaminis)' according to recently published designations of corresponding striatal constituents (Atlas of the Human Brain, 2002, Academic Press, San Diego, CA; J. Chem. Neuroanat. 23 (2002) 75).

Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood.

Gonadal steroids have remarkable developmental effects on sex-dependent brain organization and behavior in animals. Presumably, fetal or neonatal gonadal steroids are also responsible for sexual differentiation of the human brain. A limbic structure of special interest in this regard is the sexually dimorphic central subdivision of the bed nucleus of the stria terminalis (BSTc), because its size has been related to the gender identity disorder transsexuality. To determine at what age the BSTc becomes sexually dimorphic, the BSTc volume in males and females was studied from midgestation into adulthood. Using vasoactive intestinal polypeptide and somatostatin immunocytochemical staining as markers, we found that the BSTc was larger and contains more neurons in men than in women. However, this difference became significant only in adulthood, showing that sexual differentiation of the human brain may extend into the adulthood. The unexpectedly late sexual differentiation of the BSTc is discussed in relation to sex differences in developmental, adolescent, and adult gonadal steroid levels.

Fos-like immunoreactivity in brain regions of domestic rams following exposure to rams or ewes.

Limbic and basal forebrain-hypothalamic regions from male sheep differing in sexual performance were quantified for fos-like immunoreactivity. Rams classified as high-sexually performing (HP), low-sexually performing (LP), and male-oriented (MO) received noncontact sensory stimulation from either ewes in estrus (HP, n=5; LP, n=4; MO, n=4) or other males (HP, n=5; LP, n=4; MO, n=5) for a 4-h period on each of 3 consecutive days. Following exposure to stimulus animals on the third day, rams were euthanized and their brains were perfused with a 1% paraformaldehyde/1.5% glutaraldehyde solution and sections were analyzed for fos-like immunoreactivity. Brain regions analyzed were the medial amygdala (meAMY), medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), and ventromedial hypothalamic nucleus (VMH). Fos-like immunoreactivity differed between groups in the mPOA and BNST but not in the meAMY or VMH. LP rams exposed to estrous ewes had more (P<.05) neurons staining positive for fos and fos-related antigens (FRA) in the mPOA and BNST than LP rams exposed to other rams or MO rams exposed to either estrous ewes or other rams. Numbers of neurons staining positive for FRA in the mPOA and BNST of LP rams exposed to estrous ewes, however, were not different (P>.05) from HP rams exposed to either estrous ewes or other rams. The similar fos-like immunoreactivity in areas important for the display of sexual behavior in HP and LP rams may reflect similar sensory input in these two groups of rams; however, LP rams, in contrast to HP rams, do not appear to respond similarly to the same sensory stimulus.

Projections of the mediolateral part of the lateral septum to the hypothalamus, revealed by Fos expression and axonal tracing in rats.

The lateral septum participates in a variety of functions involving the hypothalamus. The present study investigated the effect of an electrical stimulation of the mediolateral part of the lateral septum on the expression of Fos in the hypothalamic nuclei by using immunohistochemical methods in anaesthetised and free-moving rats. We analysed in another series of rats the direct projections of the lateral septum by axonal anterograde tracing with biotinylated dextran-amine. Tracing was used in combination with Fos labelling in a third series of animals. Stimulation induced an expression of Fos in neurones located in anteroventral and anterodorsal preoptic nuclei, medial preoptic area, anterior hypothalamic nucleus, subparaventricular zone, dorsomedial nucleus, lateral hypothalamic area and mammillary nucleus. The distribution of Fos-immunoreactive neurones conforms to the topographic organisation of direct projections from the lateral septum, as revealed by axonal tracing. These results suggest that the lateral septum activates definite hypothalamic structures by a direct link. Some structures displayed substantial Fos labelling whereas they received a slight, or no projection, from the lateral septum. This was particularly evident in the core of the ventromedial nucleus and in areas known to contain tubero-infundibular neurones. This observation suggests that the lateral septum may also exert an indirect control, via polysynaptic links, on hypothalamic structures including nuclei involved in neuroendocrine mechanisms.

Anatomy and pathology of the septal region.

Comprising the septal area and the subcortical nuclei, the septal region is gray matter structures with widespread projection systems and different neurotransmitters. Although their function is poorly understood, lesions of the septal nuclei result in a syndrome of hyper-reactivity, amnesia, and hypersexuality. The pathologic processes affecting the septal region are discussed.