Sex difference and response to testosterone in gabaergic cells of the medial preoptic nucleus and ventral bed nuclei of the stria terminalis in gerbils

The medial preoptic nucleus (MPN) and ventral bed nuclei of the stria terminalis (BST) are needed to maintain mating in sexually experienced male gerbils and rats. The gerbil ventral BST is also activated with mating, as assessed by Fos expression, as is the medial MPN (MPNm) of both species. In gerbils, many of those mating-activated cells contain glutamic acid decarboxylase (GAD), the enzyme that synthesizes γ-aminobutyric acid (GABA). Some of those cells are projection neurons, but others may release GABA locally. Through actions in the medial preoptic area, GABA inhibits and testosterone (T) promotes male sex behavior. Thus, T may promote mating, in part, by decreasing GAD in MPNm or ventral BST cells. In rats, T increases GAD mRNA in the central MPN (MPNc), where MPN GABAergic cells are densest, but mating behavior does not change in sexually experienced males when the MPNc is ablated. Therefore, this study focused on the MPNm and ventral BST to ask whether their GABAergic cells respond to T or are sexually dimorphic. This was done by visualizing cells immunoreactive (IR) for GAD₆₇, an isoform found primarily in cell bodies, in male and female gerbils and in castrated males with and without T. At both sites, males had more GAD₆₇-IR cells than females, and T decreased GAD₆₇-IR cell numbers in males. Thus, the MPNm and ventral BST have GABAergic cells that are sexually dimorphic and in which T decreases GAD, consistent with local effects of T and GABA on mating.     

Implantation of dihydrotestosterone propionate into the lateral septum or medial amygdala facilitates copulation in castrated male rats given estradiol systemically

Two experiments were conducted to determine whether unilateral implantation of dihydrotestosterone propionate (DHTP) into different brain regions of castrated rats, bearing silastic capsules containing estradiol, could augment sexual behavior without appreciable leakage of androgen into the peripheral circulation. In Experiment 1 implanation of pulverized crystalline DHTP (via 25-gauge, 1-mm-long pellets) facilitated mating significantly without stimulating penile spine growth, provided the pellets were positioned in the lateral septum or medial amygdala. Insertion of DHTP pellets into the preoptic area-anterior hypothalamus, caudate-putamen, or the border of the substantia nigra and ventral tegmental nucleus or of cholesterol pellets into lateral septum or medial amygdala had no behavioral effects. Implanation of DHTP into the lateral septum also failed to activate penile erections in rats restrained in a supine position. In Experiment 2 implantation of different bone wax dilutions of DHTP (via 25-gauge, 1-mm-long pellets) into the preoptic area-anterior hypothalamus augmented males' sexual performance only in that group in which penile spine growth was also significantly stimulated. The results sugggst that 5α-reduced androgen is capable of activating mating in the male rat by acting locally in the lateral septum and/ or medial amygdala.     

Studies on extrahypophyseal sites of estrogen action in the induction of ovulation in rats.

To discover possible extrahypophyseal sites of estrogen action in the induction of ovulation, the influence of a s.c. injection of estradiol benzoate (EB) on cell nuclear sizes in the limbic-medial preoptic continuum of progesterone-pretreated cyclic rats was evaluated. The ovulatory dose of 5 mug EB caused a significant increase of nuclear volumes in the medial preoptic nucleus and the anterior and posterior parts of the medial amygdaloid nucleus. Precocious ovulation was induced in prepuberal female rats by unilateral implantation of a molten EB: cholesterol mixture into the posterior part of the mediocortical amygdala (PMCA), but not by implantation into the anterior part of this region (AMCA) or the medial preoptic area (MPA). In adult females injected s.c. with 2.0 mg progesterone on the day post estrus, bilateral implantation of 0.1 or 0.2 mug crystalline EB on the following day did not abolish the delaying effect of progesterone on the preovulatory LH increase and ovulation, when the implants were located in the MPA, lateral septum (LS), bed nucleus of the stria terminalis (BST), AMCA, PMCA or dorsal hippocampus (DHPC), whereas intrapituitary implants were highly effective. However, the bilateral introduction of large tallow pellets containing 0.1 mug EB each, into the LS, BST, AMCA or PMCA advanced ovulation in rats with progesterone-induced 5-day cycles. Equal pellets did neither induced ovulation nor an LH increase after implantation into the MPA or the DHPC. The results suggest that the anterior pituitary, mediocortical amygdala, BST and LS, but not the MPA or DHPC, are sites of the stimulatory feedback of estrogen on gonadotropin secretion in female rats, and that the amygdaloid response to estrogen differs between prepuberal and cyclic females.     

Distinct preoptic‐BST nuclei dissociate paternal and infanticidal behavior in mice

Paternal behavior is not innate but arises through social experience. After mating and becoming fathers, male mice change their behavior toward pups from infanticide to paternal care. However, the precise brain areas and circuit mechanisms connecting these social behaviors are largely unknown. Here we demonstrated that the c‐Fos expression pattern in the four nuclei of the preoptic‐bed nuclei of stria terminalis (BST) region could robustly discriminate five kinds of previous social behavior of male mice (parenting, infanticide, mating, inter‐male aggression, solitary control). Specifically, neuronal activation in the central part of the medial preoptic area (cMPOA) and rhomboid nucleus of the BST (BSTrh) retroactively detected paternal and infanticidal motivation with more than 95% accuracy. Moreover, cMPOA lesions switched behavior in fathers from paternal to infanticidal, while BSTrh lesions inhibited infanticide in virgin males. The projections from cMPOA to BSTrh were largely GABAergic. Optogenetic or pharmacogenetic activation of cMPOA attenuated infanticide in virgin males. Taken together, this study identifies the preoptic‐BST nuclei underlying social motivations in male mice and reveals unexpected complexity in the circuit connecting these nuclei.     

Sex differences in the level of Bcl‐2 family proteins and caspase‐3 activation in the sexually dimorphic nuclei of the preoptic area in postnatal rats

In developing rats, sex differences in the number of apoptotic cells are found in the central division of the medial preoptic nucleus (MPNc), which is a significant component of the sexually dimorphic nucleus of the preoptic area, and in the anteroventral periventricular nucleus (AVPV). Specifically, male rats have more apoptotic cells in the developing AVPV, whereas females have more apoptotic cells in the developing MPNc. To determine the mechanisms for the sex differences in apoptosis in these nuclei, we compared the expression of the Bcl‐2 family members and active caspase‐3 in postnatal female and male rats. Western blot analyses for the Bcl‐2 family proteins were performed using preoptic tissues isolated from the brain on postnatal day (PD) 1 (day of birth) or on PD8. In the AVPV‐containing tissues of PD1 rats, there were significant sex differences in the level of Bcl‐2 (female > male) and Bax (female < male) proteins, but not of Bcl‐xL or Bad proteins. In the MPNc‐containing tissues of PD8 rats, there were significant sex differences in the protein levels for Bcl‐2 (female < male), Bax (female > male), and Bad (female < male), but not for Bcl‐xL. Immunohistochemical analyses showed significant sex differences in the number of active caspase‐3‐immunoreactive cells in the AVPV on PD1 (female < male) and in the MPNc on PD8 (female > male). We further found that active caspase‐3‐immunoreactive cells of the AVPV and MPNc were immunoreactive for NeuN, a neuronal marker. These results suggest that there are sex differences in the induction of apoptosis via the mitochondrial pathway during development of the AVPV and MPNc. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

Response of ERalpha-IR and ERbeta-IR cells in the forebrain of female rats to mating stimuli

Sexual behavior in female rats depends on the action of estradiol on estrogen receptors (ERs) found in particular brain regions. While hormonal regulation of female sexual behavior requires ERalpha, the possible functions of ERbeta remain to be clarified. Mating stimulation has several behavioral and physiological consequences and induces Fos expression in many brain areas involved in the regulation of reproductive behavior and physiology. In addition, some cells in which mating induces Fos expression coexpress ERalpha. To determine whether cells in which Fos is induced by a particular mating stimulus coexpress ERalpha, ERbeta, or both, we used a triple-label immunofluorescent technique to visualize ERalpha-, ERbeta-, and mating-induced Fos-immunoreactivity (Fos-ir) in neurons in which mating stimulation reliably increases Fos expression. Ovariectomized, hormone-primed rats were either unmated, received 15 mounts, or received 15 intromissions. In the rostral medial preoptic area, Fos-ir was induced by mounts alone primarily in cells coexpressing ERalpha-ir, while Fos-ir was induced by intromissions mainly in cells coexpressing both ERalpha-ir and ERbeta-ir (ERalpha/ERbeta-ir). In the dorsal part of the posterodorsal medial amygdala, Fos-ir was induced by intromissions in cells coexpressing ERalpha-ir and ERalpha/ERbeta-ir. However, in the ventral part of the posterodorsal medial amygdala, Fos-ir was induced by intromissions primarily in cells coexpressing only ERbeta-ir. These data suggest that qualitatively different sexual stimuli may be integrated through distinct ER-containing circuits in the rostral medial preoptic area and posterodorsal medial amygdala. The diversity in coexpression of type of ER in cells in different brain areas after various mating stimuli suggests a role for both ERalpha and ERbeta in the integration of hormonal information and information related to mating stimuli.     

Ultrastructural features of the lateral preoptic area,median eminence and arcuate nucleus of the rat

Summary The arcuate nucleus, median eminence, and the lateral preoptic area from the brains of aldehyde-perfused male and female rats were examined by electron microscopy. In the lateral preoptic area, three neuronal types are described: a small light neuron, a larger light one, and a dark neuron resembling the larger light one in size and nuclear shape. Many myelinated axons are interposed among single neurons or neuronal pairs. The relationship of structures to each other is discussed. Several observations not previously reported are illustrated from tissue of the arcuate nucleus and median eminence.     

Evidence for Glutamatergic Projections from the Cochlear Nucleus to the Superior Olive and the Ventral Nucleus of the Lateral Lemniscus

Abstract: This study attempts to determine if projections ascending from the guinea pig cochlear nucleus (CN) could be glutamatergic and/or aspartatergic. Multiple radio frequency lesions were made to ablate the right CN. The ablation was verified histologically. To identify the principal targets of CN efferents, silver impregnation methods were used to localize the preterminal degeneration of fibers in transverse sections of the brainstem 5 and 7 days after CN ablation. CN efferents projected heavily to the lateral superior olive (LSO) ipsilaterally, the medial superior olive (MSO) bilaterally, and contralaterally to the medial (MNTB) and ventral (VNTB) nuclei of the trapezoid body, the ventral (VNLL) and intermediate nuclei of the lateral lemniscus and the central nucleus of the inferior colliculus (ICc). There were smaller projections to the lateral nucleus of the trapezoid body ipsilaterally, the dorsal and dorsomedial periolivary nuclei bilaterally, and the dorsal nucleus of the lateral lemniscus contralaterally. There were sparse projections to the VNLL and ICc ipsilaterally and the CN contralaterally, and a very sparse projection to the contralateral LSO. To determine if CN efferents were glutamatergic and/or aspartatergic, the fresh brainstem was sectioned transversely and samples of the LSO, MSO, MNTB, VNLL, and ICc were taken to measure the electrically evoked release and the uptake of d -[³H]Asp and [¹⁴C]Gly or [¹⁴C]GABA 3–5 days after the CN ablation. The release studies suggest that only certain of the histologically identified projections ascending from the CN may be glutamatergic and/or aspartatergic. CN ablation depressed d -[³H]Asp release in the MSO bilaterally and in the contralateral MNTB and VNLL, suggesting that the CN efferents to these nuclei may use glutamate or aspartate as a transmitter. It was unclear whether a marginal depression of d -[³H]Asp release in the ipsilateral LSO reflected the presence of glutamatergic CN projections to this nucleus. d -[³H]Asp release in the ICc was unaffected, suggesting that CN efferents to this nucleus may not be glutamatergic. There were no deficits in d -[³H]Asp uptake. [¹⁴C]Gly release from the LSO and MSO was unchanged. [¹⁴C]Gly uptake was unchanged in the MSO and depressed only in the contralateral LSO, possibly reflecting subnormal uptake activity in endings contributed by contralateral MNTB cells that had lost their CN efferents. [¹⁴C]GABA uptake in the MNTB, VNLL, and ICc was unchanged. [¹⁴C]GABA release was unchanged in the VNLL and ICc. [¹⁴C]GABA release was depressed only in the contralateral MNTB, possibly reflecting the loss of a small complement of GABAergic CN efferents and the reaction of GABAergic projections from the contralateral VNTB to their loss of CN efferents.     

Dorsal thalamic connections of the ventral lateral geniculate nucleus of rats

In order to understand better the organisation of the ventral lateral geniculate nucleus of the ventral thalamus, this paper has examined the patterns of connections that this nucleus has with various nuclei of the dorsal thalamus in rats. Injections of biotinylated dextran or cholera toxin subunit B were made into the parafascicular, central lateral, posterior thalamic, medial dorsal, lateral dorsal, lateral posterior, dorsal lateral geniculate, anterior, ventral lateral, ventrobasal and medial geniculate nuclei of Sprague-Dawley rats and their brains were processed using standard tracer detection methods. Three general patterns of ventral lateral geniculate connectivity were seen. First, the parafascicular, central lateral, medial dorsal, posterior thalamic and lateral dorsal nuclei had heavy connections with the parvocellular (internal) lamina of the ventral lateral geniculate nucleus. This geniculate lamina has been shown previously to receive heavy inputs from many functionally diverse brainstem nuclei. Second, the visually related dorsal lateral geniculate and lateral posterior nuclei had heavy connections with the magnocellular (external) lamina of the ventral lateral geniculate nucleus. This geniculate lamina has been shown by previous studies to receive heavy inputs from the visual cortex and the retina. Finally, the anterior, ventral lateral, ventrobasal and medial geniculate nuclei had very sparse, if any, connections with the ventral lateral geniculate nucleus. Overall, our results strengthen the notion that one can package the ventral lateral geniculate nucleus into distinct visual (magnocellular) and non-visual (parvocellular) components.     

The paraventriculo-infundibular corticotropin releasing factor (CRF) pathway as revealed by immunocytochemistry in long-term hypophysectomized or adrenalectomized rats

The immunocytochemical localization of corticotropin releasing factor (CRF)-containing pathways projecting from the paraventricular nucleus (PVN) to the external layer of the median eminence (ME) in long-term hypophysectomized or adrenalectomized rats is described. Immunocytochemistry was followed by silver intensification of the diaminobenzidine end-product. In comparison with untreated control rats, both hypophysectomy and adrenalectomy resulted in a dramatic increase in immunostaining of the CRF-containing perikarya and fibers, particularly those originating from the PVN and terminating in the ME. The staining was more intense in adrenalectomized than in hypophysectomized rats. The CRF-positive fibers emerging from the PVN form a medial, an intermediate and a lateral fiber pathway. The lateral and intermediate CRF tracts leave the dorsolateral part of the PVN and course laterally and medially of the fornix, respectively, then ventrally toward the optic tract. Just dorsal to the optic tract they turn in caudal direction and run parallel with and very close to the basal surface of the hypothalamus; individual fibers then turn medially to terminate in the external layer of the ME. Only a few fibers originate from the medial-ventral part of the PVN (medial pathway). These fibers run in ventral direction along the walls of the 3rd ventricle and terminate in the ME. Thus the majority of CRF fibers, similarly to other peptidergic systems, reach the medial basal hypothalamus from the anterolateral direction.     

Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat.

The central nucleus of the amygdala, bed nucleus of the stria terminalis, and central gray are important components of the neural circuitry responsible for autonomic and behavioral responses to threatening or stressful stimuli. Neurons of the amygdala and bed nucleus of the stria terminalis that project to the midbrain central gray were tested for the presence of peptide immunoreactivity. To accomplish this aim, a combined immunohistochemical and retrograde tracing technique was used. Maximal retrograde labeling was observed in the amygdala and bed nucleus of the stria terminalis after injections of retrograde tracer into the caudal ventrolateral midbrain central gray. The majority of the retrogradely labeled neurons in the amygdala were located in the medial central nucleus, although many neurons were also observed in the lateral subdivision of the central nucleus. Most of the retrogradely labeled neurons in the BST were located in the ventral and posterior lateral subdivisions, although cells were also observed in most other subdivisions. Retrogradely labeled neurotensin, corticotropin releasing factor (CRF), and somatostatin neurons were mainly observed in the lateral central nucleus and the dorsal lateral BST. Retrogradely labeled substance P-immunoreactive cells were found in the medial central nucleus and the posterior and ventral lateral BST. Enkephalin-immunoreactive retrogradely labeled cells were not observed in the amygdala or bed nucleus of the stria terminalis. A few cells in the hypothalamus (paraventricular and lateral hypothalamic nuclei) that project to the central gray also contained CRF and neurotensin immunoreactivity. The results suggest the amygdala and the bed nucleus of the stria terminalis are a major forebrain source of CRF, neurotensin, somatostatin, and substance P terminals in the midbrain central gray.     

Expression of Fos during sham sucrose intake in rats with central gustatory lesions

For humans and rodents, ingesting sucrose is rewarding. This experiment tested the prediction that the neural activity produced by sapid sucrose reaches reward systems via projections from the pons through the limbic system. Gastric cannulas drained ingested fluid before absorption. For 10 days, the rats alternated an hour of this sham ingestion between sucrose and water. On the final test day, half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes later, the rats were killed and their brains immunohistochemically stained for Fos. The groups consisted of controls and rats with excitotoxic lesions in the gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or the lateral (visceral afferent) parabrachial nucleus. In controls, compared with water, sham ingesting sucrose produced significantly more Fos-positive neurons in the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the shell of nucleus accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the ventral forebrain. After lateral PBN lesions, the Fos distributions produced by distilled H(2)O or sucrose intake did not differ from controls. Bilateral medial PBN damage, however, eliminated the sucrose-induced Fos increase not only in the TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas associated with affective responses appear to be activated directly by PBN gustatory neurons rather than via the thalamocortical taste system.     

Central connections of the olfactory bulb in the goldfish,Carassius auratus

Summary The central connections of the goldfish olfactory bulb were studied with the use of horseradish peroxidase methods. The olfactory bulb projects bilaterally to ventral and dorsolateral areas of the telencephalon; further targets include the nucleus praeopticus periventricularis and a caudal olfactory nucleus near the nucleus posterior tuberis in the diencephalon, bilaterally. The contralateral bulb and the anterior commissure also receive an input from the olfactory bulb. Contralateral projections cross in rostral and caudal portions of the anterior commissure and in the habenular commissure. Retrogradely labeled neurons are found in the contralateral bulb and in three nuclei in the telencephalon bilaterally; the neurons projecting to the olfactory bulb are far more numerous on the ipsilateral side than in the contralateral hemisphere. Afferents to the olfactory bulb are found to run almost entirely through the lateral part of the medial olfactory tract, while the bulb efferents are mediated by the medial part of the medial olfactory tract and the lateral olfactory tract. Selective tracing of olfactory sub-tracts reveals different pathways and targets of the three major tract components. Reciprocal connections between olfactory bulb and posterior terminal field suggest a laminated structure in the dorsolateral telencephalon.     

Distribution of aromatase-immunoreactive cells in the mouse forebrain

Summary The distribution of aromatase-immunoreactive cells was studied by immunocytochemistry in the mouse forebrain using a purified polyclonal antibody raised against human placental aromatase. Labeled perikarya were found in the dorso-lateral parts of the medial and tuberal hypothalamus. Positive cells filled an area extending between the subincertal nucleus in the dorsal part, the ventromedial hypothalamic nucleus in the ventral part, and the internal capsule and the magnocellular nucleus of the lateral hypothalamus in the lateral part. The same distribution was seen in the two strains of mice that were studied (Jackson and Swiss), and the number of immunoreactive perikarya did not seem to be affected by castration or testosterone treatment. No immunoreactivity could be detected in the medial regions of the preoptic area and hypothalamus; these were expected to contain the enzyme based on assays of aromatase activity performed in rats and on indirect autoradiographic evidence in mice. Our data raise questions concerning the distribution of aromatase in the brain and the mode of action of the centrally produced estrogens.     

Medullary taste responses are modulated by the bed nucleus of the stria terminalis

Previous studies have shown a modulatory influence of limbic forebrain areas, such as the central nucleus of the amygdala and lateral hypothalamus, on the activity of taste-responsive cells in the nucleus of the solitary tract (NST). The bed nucleus of the stria terminalis (BST), which receives gustatory afferent information, also sends descending axons to the NST. The present studies were designed to investigate the role of the BST in the modulation of NST gustatory activity. Extracellular action potentials were recorded from 101 taste-responsive cells in the NST of urethane-anesthetized hamsters and analyzed for a change in excitability following bilateral electrical stimulation of the BST. The response of NST taste cells to stimulation of the BST was predominately inhibitory. Orthodromic inhibitory responses were observed in 29 of 101 (28.7%) NST taste-responsive cells, with four cells inhibited bilaterally. An increase in excitability was observed in seven of the 101 (6.9%) NST taste cells. Of the 34 cells showing these responses, 25 were modulated by the ipsilateral BST and 15 by the contralateral; four were inhibited bilaterally and two inhibited ipsilaterally and excited contralaterally. The duration of inhibitory responses (mean = 177.9 ms) was significantly longer than that of excitatory responses (35.4 ms). Application of subthreshold electrical stimulation to the BST during taste trials inhibited or excited the taste responses of every BST-responsive NST cell tested with this protocol. NST neurons that were most responsive to sucrose, NaCl, citric acid or quinine hydrochloride were all affected by BST stimulation, although citric acid-best cells were significantly more often modulated and NaCl-best less often modulated than expected by chance. These results combine with excitatory and inhibitory modulation of NST neurons by the insular cortex, lateral hypothalamus and central nucleus of the amygdala to demonstrate extensive centrifugal modulation of brainstem gustatory neurons.     

Divergent axon collaterals originate in the estrogen receptive ventromedial nucleus of hypothalamus in the rat

The ventromedial nucleus of the hypothalamus (VMH) plays a crucial role in the mediation of lordosis by integrating predominantly inhibitory limbic signals with cyclic variation of ovarian steroids and sending a stimulatory output to the midbrain, especially the periaqueductal gray (PAG). Tract-tracing studies have established projections of the VMH and Golgi studies have shown these neurons to frequently give rise to axon collaterals, but the anatomical pattern of shared projections has not been explored. We have used a combination of retrograde tracers to map VMH projections to the medial division of the medial preoptic nucleus (MPNm), posterodorsal division of the medial nucleus of the amygdala (MeApd), and the PAG. Neurons with dual projections were mainly confined to the VMHvl and represented 31%–37% of each projection subset. Neurons simultaneously projecting to the MPNm, MeApd, and PAG represented 7%–9% of each projection subset. By combining tract-tracing with steroid autoradiography, we found that approximately one-quarter of each projection subset in the VMHvl concentrated ³H-estradiol. Thus, some of the VMHvl neurons that communicate a facilitatory signal to the PAG may also act to stimulate lordosis through a feedback suppression of the net inhibition formed by efferent signals from the forebrain. The even distribution of estrogen binding among projection subsets suggests a lack of compartmentalization of estrogen-regulated processes that are relevant to lordosis. 1994 John Wiley & Sons, Inc.     

Sex differences in hormonal responses of vasopressin pathways in the rat brain

Vasopressin (AVP) immunoreactivity in cells and projections of the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MA) depends on gonadal steroids. In addition, the AVP projections from the BST show denser fiber staining in males than in females. To study whether these differences depend on different hormone levels in adulthood, male and female rats were gonadectomized and similarly treated with testosterone for 4 weeks prior to sacrifice. Immunocytochemistry showed that males had significantly more AVP-immunoreactive (AVP-IR) cells in the BST and significantly denser AVP-IR projections from this nucleus to the lateral septum, lateral habenular nucleus, and periaqueductal central gray than did females. The number of AVP-IR cells in the MA nucleus was not statistically different, but denser AVP-IR fiber networks were found in the MA and ventral hippocampus, which receives its input from the MA. No differences were found in the anteroventral portion of the periventricular nucleus and the dorsomedial nucleus of the hypothalamus that receive their AVP innervation from the suprachiasmatic nucleus. These results indicate that the sex difference in the steroid-sensitive AVP pathways depends on other factors besides circulating hormone levels in adulthood.     

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen receptor alpha (ERα) cell numbers in the hypothalamus, and their relationship to sexual performance in male rats. Young (3 months) and middle-aged (12 months) rats were given sexual behavior tests, then castrated and implanted with vehicle or testosterone capsules. Rats were tested again for sexual behavior. Numbers of AR and ERα immunoreactive cells were counted in the anteroventral periventricular nucleus and the medial preoptic nucleus, and serum hormones were measured. Middle-aged intact rats had significant impairments of all sexual behavior measures compared to young males. After castration and testosterone implantation, sexual behaviors in middle-aged males were largely comparable to those in the young males. In the hypothalamus, AR cell density was significantly (5-fold) higher, and ERα cell density significantly (6-fold) lower, in testosterone- than vehicle-treated males, with no age differences. Thus, restoration of serum testosterone to comparable levels in young and middle-aged rats resulted in similar preoptic AR and ERα cell density concomitant with a reinstatement of most behaviors. These data suggest that age-related differences in sexual behavior cannot be due to absolute levels of testosterone, and further, the middle-aged brain retains the capacity to respond to exogenous testosterone with changes in hypothalamic AR and ERα expression. Our finding that testosterone replacement in aging males has profound effects on hypothalamic receptors and behavior has potential medical implications for the treatment of age-related hypogonadism in men.     

The efferent connections of the lateral septal nucleus in the guinea pig: projections to the diencephalon and brainstem

Summary The anterograde Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing technique was used to determine the distribution of efferent fibers originating in the lateral septal nucleus of the guinea pig. For complementary detection of the chemical identity of the target neurons, double-labeling immunocytochemistry was performed with antibodies to PHA-L and to vasopressin, oxytocin, vasoactive intestinal polypeptide, serotonin or dopamine -hydroxylase, respectively. The hypothalamus received the majority of the PHA-L-stained septofugal fibers. Here, a specific topography was observed. (1) The medial and lateral preoptic area, (2) the anterior, lateral, dorsal, posterior hypothalamic and retrochiasmatic area, (3) the supraoptic, paraventricular, suprachiasmatic, dorsomedial, caudal ventromedial and arcuate nuclei, and (4) the tuberomammillary, medial and lateral supramammillary, dorsal and ventral premammillary nuclei always contained PHA-L-labeled fibers. The rostral portion of the ventromedial nucleus and the medial and lateral mammillary nucleus only occasionally showed weak terminal labeling. In other diencephalic areas, termination of PHA-L-labeled fibers was observed in the epithalamus and the nuclei of the midline region of the thalamus. In the mesencephalon, terminal varicosities occurred in the ventral tegmental area, interfascicular and interpeduncular nucleus, and periaqueductal gray. In addition, the dorsal and medial raphe nuclei of the metencephalon, together with the locus coeruleus and the dorsal tegmental nucleus, received lateral septal efferents.     

The suprachiasmatic nucleus in the sheep: retinal projections and cytoarchitectural organization

The retinal innervation, cytoarchitectural, and immunohistochemical organization of the suprachiasmatic nucleus (SCN) was studied in the domestic sheep. The SCN is a large elongated nucleus extending rostrocaudally for roughly 3 mm in the hypothalamus. The morphology is unusual in that the rostral part of the nucleus extends out of the main mass of the hypothalamus onto the dorsal aspect of the optic chiasm. Following intraocular injection of wheat-germ agglutininhorseradish peroxidase or tritiated amino acids, anterograde label is distributed throughout the SCN. Retinal innervation of the SCN is bilaterally symmetric or predominantly ipsilateral. Quantitative image analysis demonstrates that, although the amount of autoradiographic label is greatest in the ventral and central parts of the nucleus, density varies progressively between different regions. In addition to the SCN, retinal fibers are also seen in the medial preoptic area, the anterior and lateral hypothalamic areas, the dorsomedial hypothalamus, the retrochiasmatic area, and the basal telencephalon. Whereas the SCN can be identified using several techniques, complete delineation of the nucleus requires combined tract tracing, cytoarchitectural, and histochemical criteria. Compared with the surrounding hypothalamic regions, the SCN contains smaller, more densely packed neurons, and is largely devoid of myelinated fibers. Cell soma sizes are smaller in the ventral SCN than in the dorsal or lateral parts, but an obvious regional transition is lacking. Using Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining, the SCN can be clearly distinguished in the rostral and medial regions, but is less differentiated toward the caudal pole. Immunohistochemical demonstration of several neuropeptides shows that the neurochemical organization of the sheep SCN is heterogeneous, but that it lacks a distinct compartmental organization. Populations of different neuropeptide-containing cells are found throughout the nucleus, although perikarya positive for vasoactive intestinal polypeptide and fibers labeled for methionine-enkephalin are predominant ventrally; neurophysine-immunoreactive cells are more prominent in the dorsal region and toward the caudal pole. The results suggest that the intrinsic organization of the sheep SCN is characterized by gradual regional transitions between different zones.