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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.

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

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.

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.

Extracellular recordings were obtained from neurons in the lateral habenular nucleus in urethane anesthetized rats. The following observations were made: (1) Action potentials of most neurons displayed a biphasic wave with an initial positivity. The interspike interval distributions were mostly unimodal. (2) The mean spontaneous firing rate was 9.2/sec with a range of 0–45/sec. (3) Following single pulse stimulation of the septum, 4 types of response pattern of lateral habenular neurons were observed: inhibition alone (23%), activation alone (9%), inhibition-activation sequence (21%), activation-inhibition sequence (10%). The majority of neurons were inhibited. Repetitive stimulation increased the total percentage of neurons being influenced. (4) Single and repetitive stimulation of the lateral preoptic area produced a similar effect on unit discharge of lateral habenular neurons as those of the septum. (5) In about 90% of the neurons, a strong convergence of both septal and preoptic influences was observed. Both synergistic and antagonistic effects of these two stimulations upon unit discharge of lateral habenular neurons were found. Interaction of the two stimulations was also studied. The effect of the interaction was dependent on the time interval between the two stimulations and the effect of the individual stimulation.

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.

Three intracranial injection parameters, injectate concentration at equivalent doses, rupture or bypass of the lateral ventricle by cannula in reaching the site, and multiple injections per animal, were studied to assess their effects on the drinking behavior elicited by angiotensin II at the lateral preoptic area (LPOA). Half of the animals were implanted with 23 gauge cannulae which penetrated the lateral ventricle en route to the site. The remaining animals received cannulae that were angled laterally to bypass the ventricle. In ventricular animals, the more concentrated injectate increased the total water intake over a 30 min period and affected the pattern of drinking through time. Animals with cannulae that penetrated the ventricle en route to the LPOA drank significantly more than the animals whose cannulae missed the ventricle. In all cases, no significant difference in drinking response was found between the first and second injections received by each rat. These results indicate that standardized intracranial chemical injection methods are needed for comparison of experiments utilizing this technique.

Male (N = 9) and female (N = 7) infant albino rats sustained bilateral lateral preoptic area (LPO) destruction on the tenth day of life. During development and as adults, these brain-damaged rats were subjected to repeated testing of drinking behaviors in response to cellular and extracellular dehydration. Immediately following LPO destruction the pups ceased suckling and most rats required tube-feeding to maintain life; however, all pups were maintaining body weight through voluntary suckling and/or feeding-drinking by 20–21 days of age. Daily water intakes were elevated from 30–42 days of age, following which intakes decreased to control volumes from 43–160 days of age. Brain damaged rats had attenuated water intakes in response to hypertonic saline injection, however these rats were hyperdipsic in response to water deprivation, polyethylene glycol injection and food deprivation treatments. These results are consistent with the suggestion that the LPO contains osmoreceptors for drinking behavior, and the present results suggest that such osmoreceptors may be functional by the tenth day of life for rats.

In the rat stimuli which increase thirst decrease feeding. This study investigated the possibility that the suppression of feeding by hypertonic saline is mediated by the preoptic area. Feeding in rats with lesions in the lateral preoptic area was suppressed by increased osmolality even though these rats did not drink to hypertonic saline. Some of these rats with lesions in the preoptic area did not drink to the extracellular thirst stimulus, isoproterenol, but feeding was suppressed by the substance. Therefore the suppression of feeding by hypertonic saline and isoproterenol can be separated from the effect of these substances on water intake. It is unlikely that the interaction between hunger and thirst takes place in the preoptic area. Hypertonic saline and isoproterenol may act on other thirst systems or directly on feeding systems to decrease food intake.

Rats with bilaterally symmetrical lesions in the laterla preoptic area do not drink after acute intracellular dehydration, but they drink normally after water deprivation. They, like normal rats, also drink more when cellular dehydration is superimposed upon water deprivation. Unlike normal rats, however, rats with lesions in the lateral preoptic area do not increase their rate of lever-pressing in response to the combined stimulus. Thus, the urge to drink can be separated from the amount of fluid drunk.

In confirmation of previous observations, lesions of the lateral preoptic area in rats abolished water ingestion during a 4-hr test following an intraperitoneal injection of hypertonic NaCl solution. However, it was observed that these animals increased their water intakes when tests were prolonged to 24 hr and drank almost exactly what they needed for osmoregulation. Furthermore, they increased their water intakes normally when NaCl was given in their diet, when NaCl was administered intravenously, or when they were water deprived and given preloads of isotonic saline to remove hypovolemia. These findings indicate that rats with lateral preoptic lesions do experience osmoregulatory thirst, and consequently, they raise new doubts about whether osmoreceptors located in the lateral preoptic area mediate thirst following the administration of osmotic loads.

The purpose of the present study was to determine if a functional or modulatory relationship exists between osmosensitive neurons of the lateral preoptic (LPO) and lateral hypothalamic (LHA) areas. Unit activity was recorded from one neural area (LPO or LHA) following bilateral destruction of the opposite area, i.e., LPO recording site with LHA lesion site, and vice-versa. Bilateral destruction of the LPO or LHA did not eliminate the osmosensitivity characteristics of LPO or LHA units, demonstrating that units of either area do not require input from the opposite area for osmosensitivity.

The effects of various hypothalamic lesions on hepatic steroid metabolism in adult rats were investigated. It was found that frontal deafferentation at the retrochiasmatic and suprachiasmatic level resulted in a complete "feminization" of hepatic steroid metabolism in male rats. Such an effect was also seen when lesions involving mainly the anterior periventricular hypothalamic area and the suprachiasmatic nucleus were performed in male rats. Midline lesions, anterior to the suprachiasmatic nucleus, on the other hand, did not result in any significant effects. A moderate degree of "feminization" was obtained after bilateral lesions involving mainly the nucleus interstitialis striae terminalis but including also parts of the anterior commissure. Small lesions in the lateral preoptic area were, however, without effect. No effects were seen of analogous lesions in female rats in any of the cases studied. The present findings suggest that a region including the anterior hypothalamic periventricular area, the suprachiasmatic nucleus and adjacent areas is involved in the control of hepatic steroid metabolism. It is postulated that the neuronal cell bodies that produce a factor with an inhibitory effect on the secretion of "feminizing factor" have their origins in this area of the hypothalamus, or, alternatively, may send axons through this area to the basal hypothalamus and thus directly or indirectly influence the anterior pituitary gland.

In this paper, the relationships between the septum and the lateral preoptic area (LPO) were demonstrated through an electrophysiological study where the patterns of responses of LPO neurons were classified. It was shown that septal (S) stimulation could induce modifications of LPO neuron responses to hypertonic NaCl, a dipsogenic stimulus. These findings suggest that the septal stimulation may partly alter thirst through a modification of LPO cell responses.

Single unit activity was recorded from a variety of brain structures after subcutaneous injection of 16 percent NaCl. Units of the lateral preoptic area (LPO), lateral hypothalamic area (LH) and tractus striohypothalamicus changed activity patterns prior to the behaviorally determined onset of drinking (5.73 min) and had estimated osmolality thresholds less than those associated with the behavioral onset of drinking (1.91 percent). Five distinct activity patterns were recorded for these osmotically sensitive cells. Units from other brain areas either showed no response or responded with activity changes not related to the onset of drinking. The role of LPO and LH cells as osmoreceptors for drinking behavior is discussed.

Recent chemical stimulation, ablation and electrophysiological recording experiments have suggested that an important osmosensitive region exists in the lateral preoptic area of the rat. The purpose of the present study was to examine the activity of single neurons in the lateral preoptic region of the rat brain in response to hypertonic, hypotonic and isotonic stimulation. Extracellular spontaneous unit discharges were recorded from 54 neurons in the lateral preoptic area of 27 hooded rats using glass micropipettes and standard recording techniques. Although frequencies of most units increased following the infusion of one or more solutions, a substantial number of units showed a decrease, while others did not appear to change. In general, the direction of change in frequency was constant for modulated responses from any given unit. The variability of the responses observed cannot be easily interpreted considering osmometric factors alone. Both osmometric and volumetric factors might be implicated in the changes observed in the activity of lateral preoptic neurons.

The central nervous structures involved in febrile responses were investigated in conscious rats by means of the 2-deoxy-D-[14C]glucose autoradiographic technique. An intravenous injection of endogenous pyrogen prepared from rabbit white blood cells induced a significant rise in the rectal temperature of rats accompanied by a decrease in the skin temperature. According to autoradiographs, significant increases in metabolic activity were observed in the lateral preoptic area, posterior part of dorsomedial thalamus, posterior hypothalamus and the red nucleus during an induced fever. Because of the close relationship between metabolic activity and brain function, these regions are considered to compose the neural components directly or indirectly related with the febrile responses.

Evoked potentials to electrical stimulation of the septum and the lateral preoptic area were recorded in the lateral habenular nucleus in urethane anesthetized rats. Evoked potentials to septal stimulation consisted of 4 components: a first positive component found to be mediated by a direct pathway via the stria medullaris; a second positive component mediated by a polysynaptic pathway with fewer synapses via the stria medullaris, the anterior, the paratenial, and the dorsomedial nuclei of the thalamus; a negative and a third positive component mediated by a polysynaptic pathway via the hippocampal commissure, the dorsal hippocampus, the stria medullaris, and the anterior, the paratenial and the dorsomedial thalamic nuclei. Evoked potentials to lateral preoptic stimulation consisted also of 4 components: a first positive component was mediated by a direct pathway via the inferior thalamic peduncle and the stria medullaris, while the other 3 were mediated by a polysynaptic pathway involving the inferior thalamic peduncle, the stria medullaris, as well as the anterior, the paratenial and the dorsomedial nuclei of the thalamus.