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Parental behavior in mammals is innate, but it is also facilitated by social experience, specifically social interactions between the parent and infant. Social interactions with infants also induce the alloparental behavior of virgin animals. Oxytocin (OT) plays an important role in mediating alloparental behavior. Although parental behavior is modulated by the medial preoptic area (MPOA) and adjacent regions, it is unclear how OT acts in these regions as a control mechanism of alloparental behavior promoted by adult-pup interaction. The aim of this study was to investigate the role of OT for facilitating effects of adult-pup interactions on alloparental behavior via neural activity of preoptic area (POA), including MPOA and adjacent area. For this purpose, we conducted behavioral tests and examined the neural activity of the OT system in POA. Virgin female mice that were repeatedly exposed to pups showed shorter retrieving latencies and higher number of c-Fos expressing neurons in POA, particular in lateral preoptic area (LPO) compared to control animals that were exposed to pups only one time. In addition, repeated pup exposure increased the proportion of OT neurons and OTR neurons expressing c-Fos in POA. The concentration of OT also significantly increased in the POA. Finally, infusion of an OT antagonist into the POA area blocked the facilitating effects of repeated pup exposure on retrieving behavior. These results demonstrated that the facilitating effects of repeated pup exposure on alloparental behavior occurred via an organizational role of the OT system.

The lateral hypothalamus (LH) includes several anatomical subregions involved in eating and reward motivation. This study explored localization of function across different LH subregions in controlling food intake stimulated by optogenetic channelrhodopsin excitation, and in supporting laser self-stimulation. We particularly compared the tuberal LH subregion, the posterior LH subregion, and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within the LH were assessed by measuring laser-induced Fos plumes and Jun plumes via immunofluorescence surrounding optic fiber tips. Those plume diameters were used to map localization of function for behavioral effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal subsection of the LH produced the most robust eating behavior and food intake initially, but produced only mild laser self-stimulation in the same rats. However, after repeated exposures to optogenetic stimulation, tuberal LH behavioral profiles shifted toward more self-stimulation and less food intake. By contrast, stimulation of the lateral preoptic area produced relatively little food intake or self-stimulation, either initially or after extended stimulation experience. Stimulation in the posterior LH subregion supported moderate self-stimulation, but not food intake, and at higher laser intensity shifted valence to evoke escape behaviors. We conclude that the tuberal LH subregion may best mediate stimulation-bound increases in food intake stimulated by optogenetic excitation. However, incentive motivational effects of tuberal LH stimulation may shift toward self-stimulation behavior after repeated stimulation. By contrast, the lateral preoptic area and posterior LH do not as readily elicit either eating behavior or laser self-stimulation, and may be more prone to higher-intensity aversive effects.

Michel Jouvet established a tradition of sleep neurophysiology that inspired several generations of sleep researchers. When I arrived in his laboratory in 1991, it was known that erection cycles occur during rapid eye movement (REM) sleep in humans. However, it was not known if such erections in sleep occurred in other species, or how REM-related erections were controlled. Employing the classical techniques and systematic approach of Jouvet and his team, I embarked on a journey of discovery. Not only were fundamental principles of REM-related erectile control identified, such as the critical role of the lateral preoptic area in the forebrain, but I also gained a deep appreciation of the scientific approach in the Jouvet tradition. Such insights passed on to his many students, together with a lifetime of friendships and collaborations, have left an indelible mark on our field.

Prolyl carboxypeptidase (PRCP), a serine protease, is widely expressed in the body including liver, lung, kidney and brain, with a variety of known substrates such as plasma prekallikrein, bradykinin, angiotensins II and III, and α-MSH, suggesting its role in the processing of tissue-specific substrates. In the brain, PRCP has been shown to inactivate hypothalamic α-MSH, thus modulating melanocortin signaling in the control of energy metabolism. While its expression pattern has been reported in the hypothalamus, little is known on the distribution of PRCP throughout the mouse brain. This study was undertaken to determine PRCP expression in the mouse brain. Radioactive in situ hybridization was performed to determine endogenous PRCP mRNA expression. In addition, using a gene-trap mouse model for PRCP deletion, X-gal staining was performed to further determine PRCP distribution. Results from both approaches showed that PRCP gene is broadly expressed in the brain.

The cytology and connections of the lateral habenula (LHb) are reviewed. The habenula is first introduced, after which the cytology of the LHb is discussed mainly with reference to cell types, general topography and descriptions of subnuclei. An overview of LHb afferent connections is given followed by some details about the projections to LHb from a number of structures. An overview of lateral habenula efferent connections is given followed by some details about the projections from LHb to a number of structures. In considering the afferent and efferent connections of the LHb some attention is given to the relative validity of regarding it as a bi-partite structure featuring ‘limbic’ and ‘pallidal’ parts. The paper ends with some concluding remarks about the relative place of the LHb in adaptive behaving.

Peciña and Berridge (2005; J Neurosci 25:11777-11786) observed that an injection of the μ-opioid receptor agonist DAMGO (D-ala(2) -N-Me-Phe(4) -Glycol(5) -enkephalin) into the rostrodorsal part of the accumbens shell (rdAcbSh) enhances expression of hedonic "liking" responses to the taste of an appetitive sucrose solution. Insofar as the connections of this hedonic "hotspot" were not singled out for special attention in the earlier neuroanatomical literature, we undertook to examine them. We observed that the patterns of inputs and outputs of the rdAcbSh are not qualitatively different from those of the rest of the Acb, except that outputs from the rdAcbSh to the lateral preoptic area and anterior and lateral hypothalamic areas are anomalously robust and overlap extensively with those of the lateral septum. We also detected reciprocal interconnections between the rdAcbSh and lateral septum. Whether and how these connections subserve hedonic impact remains to be learned, but these observations lead us to hypothesize that the rdAcbSh represents a basal forebrain transition area, in the sense that it is invaded by neurons of the lateral septum, or possibly transitional neuronal forms sharing properties of both structures. We note that the proposed transition zone between lateral septum and rdAcbSh would be but one of many in the basal forebrain and conclude by reiterating the longstanding argument that the transitional nature of such boundary areas has functional importance, of which the precise nature will remain elusive until the neurophysiological and neuropharmacological implications of such zones of transition are more generally acknowledged and better addressed.

The lateral habenular complex (LHb) constitutes an important link in the dorsal diencephalic conduction system conveying information from limbic forebrain structures to regulatory midbrain nuclei. In line with the considerable number of biological functions in which the habenula is thought to be involved, a complex subnuclear organization of the LHb has been suggested. However, the precise connectivity of habenular subnuclei remains to be identified. We hypothesize that axons from the lateral preoptic area (LPOA) project to distinct subnuclei of the LHb. As a result of an unexpected heterogeneity within the LPOA, we first examined its subregional morphology. Based on the analysis of several coronal series of sections, seven subfields were identified within the LPOA. Retrograde tracing experiments revealed that neurons projecting to the LHb were concentrated in the dorsal, ventral, and ventromedial subfields of the rostral LPOA and in the caudal LPOA. Anterograde tracing experiments confirmed that all LPOA subfields containing retrogradely labelled cells project to the LHb. Neurons in rostral subfields of the LPOA target predominantly the lateral area of the LHb, whereas caudal LPOA fibers innervate the medial LHb. Afferent labelling is most prominent within the magnocellular subnucleus in the LHbM, and only few fibers can be observed in the parvocellular subnucleus of the LHbM. The superior subnucleus of the LHbM and the oval subnucleus of the LHbL do not receive any fibers from the LPOA at all. This is the first comprehensive study so far to show that projections from LPOA subfields individually target subnuclei in the lateral habenular complex.

Made available in DSpace on 2019-09-12T16:53:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2005 We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine(8)-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG 11 antagonists (d(CH2)(5)-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl(1), 0-ET-D-Tyr(2), Val(4), Aminobutyryl(6), Arg(8.9)]-AVP (ATAVP) antagonists of V-1 and V-2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT(1) and AT(2) ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V-1, V-2, AT(2) and AT(2) receptors. (c) 2005 Elsevier B.V All rights reserved. UNESP, Sch Dent, Dept Physiol & Pathol, BR-14801903 Araraquara, SP, Brazil; , Basic Inst Biosci; UNIARA, Dept Nat & Exact Sci, Araraquara, SP, Brazil; Univ Sao Paulo, Sch Med, Dept Physiol, Ribeirao Preto, SP, Brazil; Univ Sao Paulo, Clin Hosp, BR-05508 Sao Paulo, Brazil; Publ Hosp State Sao Paulo, Dept Anesthesiol, Sao Paulo, Brazil

Sleep-related erections (SRE) naturally occur during rapid eye movement (REM) sleep, a physiological phenomenon that was previously termed nocturnal penile tumescence. In humans, these SREs occur during virtually every REM period from infancy to old age and have no relationship with dream content. Erection cycles during sleep have historically been used in the clinical setting to evaluate patients complaining of erectile dysfunction as a means to differentiate psychogenic from organic erectile failure, given the involuntary occurrence of erection cycles during sleep. Erections during REM sleep have also been documented in rats, thus establishing the first animal model for SRE research. This model has established a role for the lateral preoptic area (LPOA) in the control of erections during REM sleep. Bilateral lesions of the LPOA eliminate REM-related erections, yet leave waking-state erections intact in the rat, consistent with an emerging view that the higher central mechanisms of erections may be context specific.

This experiment investigated the existence of a direct anatomical connection between lateral preoptic and ventral tegmental areas that mediate brain stimulation reward using the behavioral adaptation of the collision test. This test is a double-pulse, two-electrode technique based on the axonal conduction failure that occurs when two separate sites in the same axon bundle are concurrently stimulated. This anatomical arrangement is inferred from the shape of the function relating the effectiveness of double-pulse stimulation to the interval between pulses. In this study, nine rats with a total of 44 pairs of sites were examined. In two pairs only was there a profile suggestive of an axonal collision effect, while the double-pulse effectiveness curve consistent with the properties of transynaptic collision was apparent for a single pair of sites; the remaining 93% were associated with relatively flat effectiveness curves. While electrode misalignment could be responsible for these results, there was adequate sampling to suggest that the preponderance of first stage signals that give rise to the rewarding effects mediated by the lateral preoptic and ventral tegmental areas do not travel along the same fiber bundle. However, stimulation applied to both sites concurrently produces a summation that is roughly 40% greater than stimulation at either site alone, suggesting reasonable integration of the reward signals generated by lateral preoptic and ventral tegmental area stimulation.

Given the putative role of the lateral preoptic area as a primary contributor of the cell bodies of origin of the descending pathway linking a subset of lateral hypothalamic and ventral tegmental area reward neurons, the distribution of self-stimulation sites in this structure was mapped in 22 animals using moveable electrodes and threshold procedures. Ninety-seven electrode sites were evaluated with placements ranging from just rostral to the midline convergence of the anterior commissure back to the transition zone between the lateral preoptic and lateral hypothalamic areas; of these, roughly 2/3 supported self-stimulation which was widely observed throughout the lateral preoptic area and medial forebrain bundle. In general, self-stimulation thresholds obtained from lateral sites were most stable, and progressively so approaching more caudal regions. Examination of the slopes of the period/current trade-off functions revealed a tendency for higher values in lateral and caudal sites; in contrast, dorsoventral excursions did not influence these estimates. Taken together, these data provide support for the notion that the substrate for brain-stimulation reward in the lateral preoptic area has a relatively homogeneous distribution that is more diffusely organized than that found in reward sites activated further caudally in the medial forebrain bundle.

Peripheral administration of lipopolysaccharide (LPS) is associated with alterations in sleep and the electroencephalogram. To evaluate potential neuronal mechanisms for the somnogenic effects of LPS administration, we used unanesthetized rats to survey the firing patterns of neurons in various regions of rat basal forebrain (BF) and hypothalamus during spontaneous sleep and waking and during the epochs of sleep and waking that occurred after the intraperitoneal administration of LPS. In the brain regions studied, LPS administration was associated with altered firing rates in 39% of the neurons examined. A larger proportion of LPS-responsive units showed vigilance-related alterations in firing rates compared with nonresponsive units. Approximately equal proportions of LPS-responsive neurons showed increased and decreased firing rates after LPS administration, with some units in the lateral preoptic area of the hypothalamus showing particularly robust increases. These findings are consistent with other studies showing vigilance-related changes in neuronal activity in various regions of BF and hypothalamus and further demonstrate that peripheral LPS administration alters neuronal firing rates in these structures during both sleep and waking.

The acute self-stimulation of the medial forebrain bundle was reported to induce the expression of c-Fos, the protein product of c-fos , an immediate early gene, in the central nervous system. In the present study, we examined regional changes in c-Fos expression in several reward-related areas of rat brain in response to short- and long-term exposure to self-stimulation of the medial forebrain bundle. Short-term one-hour stimulation of the medial forebrain bundle for one day after training, which evoked steady self-stimulation behavior, significantly increased the number of c-Fos-positive neurons bilaterally in all of 15 brain structures assayed, as compared to the non-stimulation control. Among them, structures showing a larger number of the stained neurons on the stimulated side were the anterior olfactory nucleus, amygdala, medial caudate–putamen complex, lateral septum, bed nucleus of the stria terminals, ventral pallidum, substantia innominata, lateral preoptic area, medial preoptic area, lateral hypothalamus rostral to the stimulating electrodes, and substantia nigra. Long-term stimulation of the medial forebrain bundle once daily for five successive days, which maintained consistently stable self-stimulation behavior, also increased the number of c-Fos-positive neurons in the aforementioned structures, as compared to the control. However, the long-term rewarding stimulation diminished the increased number of labeled neurons, as compared to the short-term rewarding stimulation. Seven areas, medial caudate–putamen complex, ventral pallidum, substantia innominata, lateral preoptic area, medial preoptic area, rostral lateral hypothalamus and substantia nigra, showed asymmetrical, ipsilateral predominance after the short- and long-term stimulation. However, the stained neuron count in those areas after the long-term stimulation was reduced to less than 50% of that found after the short-term stimulation with the exception of lateral preoptic area and rostral lateral hypothalamus. The results suggest that the development of desensitization of c-Fos response may differ among the reward-relevant brain regions as a consequence of repeated self-stimulation. They also indicate that a larger portion of neurons in the lateral preoptic area and rostral lateral hypothalamus may be implicated in both short- and long-term self-stimulations of the medial forebrain bundle.

Research report; International audience; Associative learning contributes crucially to adjust the behavior of neonates to the permanently changing environment. In the European rabbit, the mammary pheromone (MP) excreted in milk triggers sucking behavior in newborns, and additionally promotes very rapid learning of initially neutral odor cues. Such stimuli become then as active as the MP itself to elicit the orocephalic motor responses involved in suckling. In this context, the rabbit is an interesting model to address the question of brain circuits early engaged by learning and memory. Here, we evaluated the brain activation (olfactory bulb and central regions) induced in 4-day-old pups by an odorant (ethyl acetoacetate, EAA) after single pairing with the MP and its subsequent acquired ability to elicit sucking-related behavior (conditioned group) or after mere exposure to EAA alone (unconditioned group). The brain-wide mapping of c-Fos expression was used to compare neural activation patterns in both groups. Evidence of high immunostaining to odorant EAA occurred in the mitral+granule cells layer of the main olfactory bulb in pups previously exposed to EAA in association with the MP. These pups also showed higher expression of Fos in the piriform cortex, the hypothalamic lateral preoptic area and the amygdala (cortical and basal nuclei). Thus, MP-induced odor learning induces rapid brain modifications in rabbit neonates. The cerebral framework supporting the acquisition appears however different compared to the circuit involved in the processing of the MP itself.

The mechanisms underlying the sleep-states periodicity in animals are a mystery of biology. Recent studies identified a new neuronal population activated during the slow wave sleep (SWS) in the ventral lateral preoptic area of the hypothalamus. Interactions between this neuronal population and the others populations implicated in the vigilance states (paradoxical sleep (PS) and wake (W)) dynamics are not determined. Thus, we propose here a sleep–waking theoretical model that depicts the potential interactions between the neuronal populations responsible for the three vigilance states. First, we pooled data from previous papers regarding the neuronal populations firing rate time course and characterized statistically the experimental hypnograms. Then, we constructed a nonlinear differential equations system describing the neuronal populations activity time course. A simple rule playing the firing threshold role applied to the model allows to construct a theoretical hypnogram. A random modulation of the neuronal activity, shows that theoretical hypnograms present a dynamics close to the experimental observations. Furthermore, we show that the wake promoting neurons activity can predict the next SWS episode duration.

Using an indirect immunoperoxidase technique, the location of cell bodies and fibres containing adrenocorticotropin hormone/corticotropin-like intermediate lobe peptide (ACTH/CLIP) was studied in the cat diencephalon. Immunoreactivity was observed in several diencephalic nuclei of the cat in which no immunoreactivity has been previously reported. In this sense, a low density of immunoreactive cell bodies was found in the nucleus ventromedialis hypothalami; a high density of immunoreactive fibres was found in the medial preoptic area; a moderate density in the lateral preoptic area and in the nuclei centralis thalami (pars medialis), interventralis thalami, interanteromedialis thalami, parafascicularis and praemamillaris (pars ventralis and pars dorsalis); a low density in the nuclei habenularis lateralis and reuniens thalami, and single fibres were found in the nuclei lateralis thalami (pars anterior), habenularis medialis, parataenialis, corpus geniculatum mediale, ventralis thalami (pars medialis) and in the fornix. Our results point to a more widespread distribution of ACTH/CLIP immunoreactive structures in the cat diencephalon in comparison with previous studies carried out in the same region of this feline.

Animals barpressing for rewarding electrical stimulation of the lateral preoptic area typically had well-developed motor seizures during their first self-stimulation session. Over subsequent daily testing, however, the incidence of self-induced seizures decreased significantly. In a second experiment, externally controlled delivery of stimulation was not found to induce a high proportion of first-session seizures but, over repeated daily sessions, there was a significant increase in elicited seizures. The rapid development of the first-session seizures is attributed to the highly potentiating consequences of the pattern of self-stimulation. The decrease in seizures over repeated daily self-stimulation testing is suggested to reflect learned avoidance of self-induced seizures.

Electrical self-stimulation in the lateral hypothalamus of both hemispheres was recorded in 14 rats before and after administration of a unilateral ibotenic acid lesion of the cell bodies in the region of the lateral preoptic area. A significant decrease in the rate of self- stimulation at each of two stimulation intensities was found when the electrode was placed in the hemisphere in which the ibotenic acid lesion was made. This decrease remained constant over 21 days of testing. No changes were detected in rate of self-stimulation in the intact contralateral hemisphere. These results provide evidence for a role in lateral hypothalamic self-stimulation of intrinsic neurons located in the region of the lateral preoptic area.

A 10 ng dose of angiotensin injected into the lateral preoptic area of the brain induces drinking and suppresses feeding in 24 hr food-deprived rats. The induction of drinking is reduced, and the suppression of feeding abolished, by a 15 ml intragastric preload of water, or of isotonic saline. The results are interpreted as showing that suppression of feeding by angiotensin is due to inhibition of feeding by a central thirst factor.

Extracellular recordings were made from single neurons in the lateral habenular nucleus of urethane-anesthetized rats. Single pulse stimulation of the entopeduncular nucleus influenced the spontaneous activity of 200 out of 293 (68%) lateral habenular neurons tested, with the most frequent response being suppression of activity and initial activation followed by suppression. Single pulse stimulation of the lateral preoptic area influenced the activity of 140 out of 165 (85%) lateral habenular neurons tested. Responses were similar to those for entopeduncular stimulation. In a series of 137 lateral habenular units, 85 (62%) were influenced by stimulation of both sites indicating convergence of inputs from these two forebrain areas. Approximately half of the lateral habenular neurons which received converging inputs from entopeduncular nucleus and lateral preoptic area were activated antidromically by stimulation of the fasciculus retroflexus, indicating that they were output neurons. These electrophysiological findings support the suggestion from recent neuroanatomical studies that the lateral habenular nucleus is a site of integration for entopenduncular and limbic inputs and in turn sends signals to the midbrain.

For the first time, brain-recording data were brought to bear directly on the question of a critical osmosensitive zone in the lateral preoptic area as specifically delimited in the rat by Blass and Epstein, and in the rabbit by Peck and Novin. Our data clearly showed that this critical zone in the lateral preoptic area of the rat contains cells that are osmosensitive. Simultaneous recording from cell populations (a) inside the critical zone and (b) in a zone medial to it showed that the net acceleratory response to challenge for the former was much greater than it was for the latter. These findings constitute new evidence for the critical importance of the lateral preoptic area in cellular dehydration thirst.

The projections of the stria terminalis were traced with the Fink-Heimer stain following lesions at the level of the anterior commissure. The pre-commissural stria terminalis is amygdalofugal only, and projects to the nucleus of the anterior commissure, the medial preoptic area, the ventral portion of the capsule surrounding the ventromedial nucleus, and to the area closely adjacent to the periventricular nucleus by way of the medial corticohypothalamic tract. The postcommissural stria terminalis is both amygdalofugal and amygdalopetal. Its hypothalamic projection is to the lateral preoptic area and the bed nucleus of the stria terminalis, and to the lateral hypothalamus by way of the lateral preoptic area. The amygdaloid projection is mainly to the basolateral nucleus, with fewer terminations to the basomedial nucleus and the area surrounding the central nucleus. The projections of the bed nucleus of the stria terminalis are quite similar to the postcommissural stria, except for an additional projection to the magnocellular paraventricular and dorsal periventricular nuclei by way of the lateral filiform tract. The commissural stria terminalis projects contralaterally to cells within its fiber bundle and the posterior limb of the anterior commissure.

Horseradish peroxidase, 30% Sigma Type VI, was administered iontophoretically to the lateral preoptic area (LPA) and lateral hypothalamus (LH) of male hooded rats. Animals were perfused intracardially on the following day, brains were removed and later sliced into 30–50 μm sections and processed with DAB and BDH for the brown and blue reaction products. Both LPA and LH ejections of horseradish peroxidase (HRP) resulted in the extensive labeling of soma and axons along the entire extent of the LPA, LH and the medial forebrain bundle (MFB). In addition, ejections in both areas resulted in similar labeling in the nucleus accumbens, stria hypothalamic tract, stria terminalis, medial hypothalamic area, amygdaloid nuclei, and the zona incerta. These results demonstrate a considerable degree of interconnectivity within the LPA and LH along the entire extent of the MFB and that presynaptic inputs from other adjacent hypothalamic and limbic areas terminate on neurons in the LPA-LH-MFB neuropil.