Accessory mammillary bodies formed by the enlarged lateral mammillary nuclei: cytoarchitecture.

Post mortem examination of the hypothalamus of a 79-year-old woman, deceased in cardiac arrest without recorded neurological symptoms, revealed well-defined spherical protrusions located rostro-laterally to the mammillary bodies that appear to be regular size when compared to normal. Cytoarchitectonically, these accessory mammillary bodies are formed by the enlarged lateral mammillary nucleus that is normally a thin shell over the medial. The mammillary nuclei appear to function synergistically in memory formation in rats; however, the functional consequences of the present variation are difficult to interpret due to lack of human data. Most importantly, in addition to the possible functional consequences, lateral mammillary bodies can be falsely identified as various neuropathological processes of the basal diencephalon including gliomas; therefore, it is extremely important to disseminate this unique morphological variant among clinicians.

Characterization of McDonald's intermediate part of the Central nucleus of the amygdala in the rat.

The actual organization of the central nucleus of the amygdala (CEA) in the rat is mostly based on cytoarchitecture and the distribution of several cell types, as described by McDonald in 1982. Four divisions were identified by this author. However, since this original work, one of these divisions, the intermediate part, has not been consistently recognized based on Nissl-stained material. In the present study, we observed that a compact condensation of retrogradely labeled cells is found in the CEA after fluorogold injection in the anterior region of the tuberal lateral hypothalamic area (LHA) in the rat. We then searched for neurochemical markers of this cell condensation and found that it is quite specifically labeled for calbindin (Cb), but also contains calretinin (Cr), tyrosine hydroxylase (TH) and methionine-enkephalin (Met-Enk) immunohistochemical signals. These neurochemical features are specific to this cell group which, therefore, is distinct from the other parts of the CEA. We then performed cholera toxin injections in the mouse LHA to identify this cell group in this species. We found that neurons exist in the medial and rostral CEAl that project into the LHA but they have a less tight organization than in the rat.

The role of melanin concentrating hormone (MCH) in the central chemoreflex: a knockdown study by siRNA in the lateral hypothalamus in rats.

Melanin concentrating hormone (MCH), a neuropeptide produced mainly in neurons localized to the lateral hypothalamic area (LHA), has been implicated in the regulation of food intake, energy balance, sleep state, and the cardiovascular system. Hypothalamic MCH neurons also have multisynaptic connections with diaphragmatic motoneurons and project to many central chemoreceptor sites. However, there are few studies of MCH involvement in central respiratory control. To test the hypothesis that MCH plays a role in the central chemoreflex, we induced a down regulation of MCH in the central nervous system by knocking down the MCH precursor (pMCH) mRNA in the LHA using a pool of small interfering RNA (siRNA), and measured the resultant changes in breathing, metabolic rate, body weight, and blood glucose levels in conscious rats. The injections of pMCH-siRNA into the LHA successfully produced a ∼ 62% reduction of pMCH mRNA expression in the LHA and a ∼ 43% decrease of MCH levels in the cerebrospinal fluid relative to scrambled-siRNA treatment (P = 0.006 and P = 0.02 respectively). Compared to the pretreatment baseline and the scrambled-siRNA treated control rats, knockdown of MCH resulted in: 1) an enhanced hypercapnic chemoreflex (∼ 42 & 47% respectively; P < 0.05) only in wakefulness; 2) a decrease in body weight and basal glucose levels; and 3) an unchanged metabolic rate. Our results indicate that MCH participates not only in the regulation of glucose and sleep-wake homeostasis but also the vigilance-state dependent regulation of the central hypercapnic chemoreflex and respiratory control.

Voluntary enhancement of neural signatures of affiliative emotion using FMRI neurofeedback.

In Ridley Scott's film "Blade Runner", empathy-detection devices are employed to measure affiliative emotions. Despite recent neurocomputational advances, it is unknown whether brain signatures of affiliative emotions, such as tenderness/affection, can be decoded and voluntarily modulated. Here, we employed multivariate voxel pattern analysis and real-time fMRI to address this question. We found that participants were able to use visual feedback based on decoded fMRI patterns as a neurofeedback signal to increase brain activation characteristic of tenderness/affection relative to pride, an equally complex control emotion. Such improvement was not observed in a control group performing the same fMRI task without neurofeedback. Furthermore, the neurofeedback-driven enhancement of tenderness/affection-related distributed patterns was associated with local fMRI responses in the septohypothalamic area and frontopolar cortex, regions previously implicated in affiliative emotion. This demonstrates that humans can voluntarily enhance brain signatures of tenderness/affection, unlocking new possibilities for promoting prosocial emotions and countering antisocial behavior.

Forebrain GABAergic projections from the dorsal raphe nucleus identified by using GAD67-GFP knock-in mice.

The dorsal raphe nucleus (DR) contains serotonergic (5-HT) neurons that project widely throughout the forebrain. These forebrain regions also receive innervation from non-5-HT neurons in the DR. One of the main groups of non-5-HT neurons in the DR is γ-aminobutyric acid (GABA)ergic, but their projections are poorly understood due to the difficulty of labeling these neurons immunohistochemically. To identify GABAergic projection neurons within the DR in the current study, we used a knock-in mouse line in which expression of green fluorescent protein (GFP) is controlled by the glutamic acid decarboxylase (GAD)67 promotor. Projections of GAD67-GFP neurons to the prefrontal cortex (PFC), nucleus accumbens (NAC), and lateral hypothalamus (LH) were evaluated by using retrograde tract tracing. The location of GAD67-GFP neurons projecting to each of these areas was mapped by rostrocaudal and dorsoventral location within the DR. Overall, 16% of DR neurons projecting to either the PFC or NAC were identified as GAD67-GFP neurons. GAD67-GFP neurons projecting to the PFC were most commonly found ventrally, in the rostral two-thirds of the DR. NAC-projecting GAD67-GFP neurons had an overlapping distribution that extended dorsally. GAD67-GFP neurons made a larger contribution to the projection of the DR to the LH, accounting for 36% of retrogradely labeled neurons, and were widespread throughout the DR. The current data indicate that DR GABAergic neurons not only may have the capacity to influence local network activity, but also make a notable contribution to DR output to multiple forebrain targets. J. Comp. Neurol. 520:4157-4167, 2012. © 2012 Wiley Periodicals, Inc.

Connections of the lateral hypothalamic area juxtadorsomedial region in the male rat.

The connections of the lateral hypothalamic area juxtadorsomedial region (LHAjd) were investigated in a series of pathway-tracing experiments involving iontophoretic co-injection of the tracers Phaseolus vulgaris-leucoagglutinin (PHA-L; for outputs) and cholera toxin B subunit (CTB; for inputs). Results revealed that the LHAjd has connections with some 318 distinct gray matter regions encompassing all four subsystems-motor, sensory, cognitive, and behavioral state-included in a basic structure-function network model of the nervous system. Integration of these subsystems is necessary for the coordination and control of emotion and behavior, and in that regard the connections of the LHAjd indicate that it may have a prominent role. Furthermore, the LHAjd connections, together with the connections of other LHA differentiations studied similarly to date, indicate a distinct topographic organization that suggests each LHA differentiation has specifically differing degrees of involvement in the control of multiple behaviors. For the LHAjd, its involvement to a high degree in the control of defensive behavior, and to a lesser degree in the control of other behaviors, including ingestive and reproductive, is suggested. Moreover, the connections of the LHAjd suggest that its possible role in the control of these behaviors may be very broad in scope because they involve the somatic, neuroendocrine, and autonomic divisions of the nervous system. In addition, we suggest that connections between LHA differentiations may provide, at the level of the hypothalamus, a neuronal substrate for the coordinated control of multiple themes in the behavioral repertoire.

The lateral hypothalamic parvalbumin-immunoreactive (PV1) nucleus in rodents.

In the lateral hypothalamus, groups of functionally related cells tend to be widely scattered rather than confined to discrete, anatomically distinct units. However, by using parvalbumin (PV)-specific antibodies, a solitary, compact cord of PV-immunoreactive cells (the PV1-nucleus) has been identified in the ventrolateral tuberal hypothalamus in various species. Here we describe the topography, the chemo-, cyto-, and myeloarchitectonics, and the ultrastructure of this PV1-nucleus in rodents. The PV1-nucleus is located within the ventrolateral division of the medial forebrain bundle. In the horizontal plane, it has a length of 1 mm in mice and 2 mm in rats. PV-immunoreactive perikarya fall into two distinct size categories and number (~800 in rats and ~400 in mice). They are intermingled with PV-negative neurons and coarse axons of the medial forebrain bundle, some of which are PV-positive. Symmetric and asymmetric synapses, as well as PV-positive and PV-negative fiber endings, terminate on the perikarya of both PV-positive and PV-negative neurons. PV-positive neurons of the PV1-nucleus express glutamate, not γ-aminobutyric acid (GABA), the neurotransmitter that is usually associated with PV-containing nerve cells. Although we could not find evidence that PV1 neurons express either catecholamines or known neuropeptides, they sometimes are interspersed with the fibers and terminals of such cells. From its analogous topographical situation, the PV1-nucleus could correspond to the lateral tuberal nucleus in humans. We anticipate that the presence of the marker protein PV in the PV1-nucleus of the rodent hypothalamus will facilitate future studies relating to the connectivity, transcriptomics, and function of this entity.

Stimulation of lateral hypothalamic AMPA receptors may induce feeding in rats.

Glutamate or its ionotropic receptor (iGluR) agonists, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxale propionate (AMPA), and kainate (KA) elicit feeding when microinjected into the lateral hypothalamus (LH) of satiated rats. In the present study we investigated the contributions of AMPA and KA receptors (AMPARs and KARs) to feeding initiation. Intense feeding was elicited by LH injection of RS-AMPA (1 and 10 nmol) but not by the isolated, inactive R-AMPA enantiomer (1 and 10 nmol). Further, LH pretreatment with either the non-selective AMPAR/KAR antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 4 nmol) or the selective AMPAR antagonist, GYKI 52466 (10 nmol), suppressed AMPA-elicited food intake and, when combined, blocked AMPA-elicited food intake. These findings suggest that LH AMPARs mediate AMPA injection-elicited feeding with a possible contribution by KARs. In contrast, CNQX or GYKI 52466 injected into the LH at the onset of the nocturnal period or into fasted rats did not suppress the feeding produced by either condition. RS-AMPA injected into the LH of fasted or nocturnal feeding subjects elicited eating in both conditions; however, the magnitude of the increase was greater in fasted rats. These data suggest that selective stimulation of AMPAR in the LH is sufficient to elicit feeding. In contrast, the results did not provide evidence that AMPAR stimulation is necessary for deprivation-induced or nocturnal eating; however, they did suggest that modulatory interactions may exist between these receptors and these forms of naturally occurring eating behavior.

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat.

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.

Orexin/hypocretin modulation of the basal forebrain cholinergic system: Role in attention.

The basal forebrain cholinergic system (BFCS) plays a role in several aspects of attentional function. Activation of this system by different afferent inputs is likely to influence how attentional resources are allocated. While it has been recognized for some time that the hypothalamus is a significant source of projections to the basal forebrain, the phenotype(s) of these inputs and the conditions under which their regulation of the BFCS becomes functionally relevant are still unclear. The cell bodies of neurons expressing orexin/hypocretin neuropeptides are restricted to the lateral hypothalamus and contiguous perifornical area but have widespread projections, including to the basal forebrain. Orexin fibers and both orexin receptor subtypes are distributed in cholinergic parts of the basal forebrain, where application of orexin peptides increases cell activity and cortical acetylcholine release. Furthermore, disruption of orexin signaling in the basal forebrain impairs the cholinergic response to an appetitive stimulus. In this review, we propose that orexin inputs to the BFCS form an anatomical substrate for links between arousal and attention, and that these interactions might be particularly important as a means by which interoceptive cues bias allocation of attentional resources toward related exteroceptive stimuli. Dysfunction in orexin-acetylcholine interactions may play a role in the arousal and attentional deficits that accompany neurodegenerative conditions as diverse as drug addiction and age-related cognitive decline.

The medial forebrain bundle mediates cardiovascular responses to electrical stimulation of the medial prefrontal cortex.

The medial prefrontal cortex (MPFC) is involved in cardiovascular control. MPFC electrical stimulation has been reported to cause depressor and bradycardic responses in anesthetized rats. Although the pathway involved is yet unknown, there is evidence indicating the existence of a relay in the lateral hypothalamus (LH). The medial forebrain bundle (MFB) that courses in the lateral portion of the LH carries the vast majority of telencephalic afferent as well efferent projections, including those from the MPFC. To evaluate if the hypotensive pathway originating in the MPFC courses the MFB, we studied the effect of coronal or sagittal knife cuts through the LH and other brain areas on the cardiovascular responses to MPFC electrical stimulation. Knife cuts were performed using blades 1 to 6 mm wide. Results indicate that the neural pathway descending from the MFB decussates early in the vicinity of MPFC, crossing the midline within the corpus callosum and yielding two descending pathways that travel rostro-caudally in the lateral portion of the LH, within the MFB. The decussation was confirmed by histological analysis of brain sections processed after the injection of biotinilated dextran amine in the site of the stimulation in the MPFC. Because knife cuts through the LH ipsilateral had minimal effects on the cardiovascular responses and knife cuts performed contralateral to the stimulated MPFC had no effect on the response to MPFC stimulation, data indicate that the contralateral limb of the pathway may be only activated as an alternative pathway when the ipsilateral pathway is blocked.

The role of histamine on cognition.

Histamine was intensively studied at the beginning of the 20th century because of its important role in allergic and inflammation processes. In those days it was very difficult that researchers could envisage another impacting function for the imidazolamine in the living systems. Once the imidazolamine was found located in neuron compartment in the brain, increasing evidence supported many regulatory functions including its possible role in memory and learning. The specific participation of histamine in cognitive functions followed a slow and unclear pathway because the many different experimental learning models, pharmacologic approaches, systemic and localized applications of the histamine active compounds into the brain used by researchers showed facilitating or inhibitory effects on learning, generating an active issue that has extended up to present time. In this review, all these aspects are analyzed and discussed considering the many intracellular different mechanisms discovered for histamine, the specific histamine receptors and the compartmentalizing proprieties of the brain that might explain the apparent inconsistent effects of the imidazolamine in learning. In addition, a hypothetical physiologic role for histamine in memory is proposed under the standard theories of learning in experimental animals and humans.

Lateral hypothalamic-induced alpha-adrenoceptor modulation occurs in a model of inflammatory pain in rats.

Previous work from our lab showed that stimulation of the lateral hypothalamus (LH) produces analgesia (antinociception) in a model of thermal nociceptive pain. This antinociceptive effect is mediated by alpha2-adrenoceptors in the spinal cord dorsal horn. However, a concomitant, opposing hyperalgesic (pro-nociceptive) response also occurs, which is mediated by alpha1-adrenoceptors in the dorsal horn. Antinociception predominates but is attenuated by the pronociceptive response. To determine whether such an effect occurs in a model of inflammatory pain, we applied mustard oil (allyl isothiocyanate; 20 microl) to the left ankle of female Sprague-Dawley rats. We then stimulated the LH using carbamylcholine chloride (carbachol; 125 nmol). The foot withdrawal latencies were measured. Some rats received intrathecal alpha-adrenoceptor antagonists to determine whether the opposing alpha-adrenoceptor response was present. Mustard oil application produced hyperalgesia in the affected paw, while the LH stimulation increased the foot withdrawal latencies for the mustard oil paw as compared to the control group. Following carbachol microinjection in the LH, WB4101, an alpha1-adrenoceptor antagonist, produced significantly longer foot withdrawal latencies compared to saline controls, while yohimbine, an alpha2-antagonist, decreased the foot withdrawal latencies from 10 min postinjection (p < .05). These findings support the hypothesis that the LH-induced nociceptive modulation is mediated through an alpha-adrenoceptor opposing response in a model of inflammatory pain.

Terminal field specificity of forebrain efferent axons to brainstem gustatory nuclei.

Rostral forebrain structures like the gustatory cortex (GC), bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and lateral hypothalamus (LH) send projections to the nucleus of solitary tract (NST) and the parabrachial nucleus (PBN) that modulate taste-elicited responses. However, the proportion of forebrain-induced excitatory and inhibitory effects often differs when taste cell recording changes from the NST to the PBN. The present study investigated whether this descending influence originates from a shared or distinct population of forebrain neurons. Under electrophysiological guidance, the retrograde tracers fast blue (FB) and fluorogold (FG) or green (GFB) and red (RFB) fluorescent latex microbeads were injected iontophoretically or by pressure pulses (10 ms at 20 psi) into the taste-responsive regions of the NST and the ipsilateral PBN in six rats. Seven days later, the animals were euthanized and tissue sections containing the LH, CeA, BNST, and GC were processed for co-localization of FB and FG or GFB and RFB. The results showed that the CeA is the major source of input to the NST (82.3+/-7.6 cells/section) and the PBN (76.7+/-11.5), compared to the BNST (31.8+/-4.5; 37.0+/-4.8), the LH (35.0+/-5.4; 33.6+/-5.7), and the GC (27.5+/-4.0; 29.0+/-4.6). Of the total number of retrogradely labeled cells, the incidence of tracer co-localization was 17+/-3% in the GC, 17+/-2% in the CeA, 15+/-3% in the BNST and 16+/-1% in the LH. Thus, irrespective of forebrain source the majority of descending input to the gustatory NST and PBN originates from distinct neuronal populations. This arrangement provides an anatomical substrate for differential modulation of taste processing in the first and second central relays of the ascending gustatory system.

Differential expression of hypothalamic CART mRNA in response to body weight change following different dietary interventions.

Cocaine- and amphetamine-regulated transcript (CART) peptide is widely expressed in the hypothalamus and is involved in the central regulation of energy balance. Using in situ hybridization, this study examined the roles of CART peptide in the hypothalamus of diet-induced obese (DIO) or diet-resistant (DR) mice under different dietary interventions including high-fat (HF), low-fat (LF) and pair-feeding (PF) diet for 6 weeks. Pair feeding the energy intake of the DIO and DR mice was used to determine whether there is an inherent difference in baseline CART expression that may cause the DIO and DR phenotypes. The results demonstrated that CART mRNA expression in the hypothalamus of the DIO mice responded differently on the high-fat diet compared to DR mice. The arcuate nucleus and paraventricular nucleus showed a significant reduction in CART mRNA expression in DIO mice compared to DR mice on the HF diet (-19.6%, p=0.019; -26.1%, p=0.003); whilst a profound increase in CART mRNA expression was observed in the dorsomedial nucleus and lateral hypothalamic area (+44.5%, p=0.007; +37.4%, p=0.033). Our study suggests that the decrease of CART mRNA expression in Arc and PVN regions of DIO mice may contribute to the development of high-fat diet-induced obesity. In addition, CART in the dorsomedial nucleus (DM) of hypothalamus and lateral hypothalamus (LH) may be involved in the activation of an orexigenic effect. Since pair feeding of the high-fat diet eliminated both the body weight and CART mRNA differences between the DIO and DR mice, it is likely that their alterations in gene expression were a consequence of their dissimilar body weight levels.

Caudal hindbrain lactate infusion alters glucokinase, SUR1, and neuronal substrate fuel transporter gene expression in the dorsal vagal complex, lateral hypothalamic area, and ventromedial nucleus hypothalamus of hypoglycemic male rats.

While in vitro studies show that the oxidizable energy substrate, lactate, is a preferred fuel for CNS neurons during states of energy crisis, and that lactate may regulate neuronal glucose uptake under those conditions, its role in neuronal function in vivo remains controversial. Glucose-excited neurons in hindbrain dorsal vagal complex (DVC) monitor both glucose and lactate, and express both the glucose sensor, glucokinase (GK), and the SUR1 subunit of the plasma membrane energy transducer, K(ATP). Fourth ventricular lactate infusion exacerbates insulin-induced hypoglycemia (IIH) and IIH-associated patterns of DVC neuronal activation. We investigated the hypothesis that during glucoprivation, lactate regulates neuronal monocarboxylate and glucose transporter gene transcription in the DVC, and adjustments in these gene profiles are correlated with altered GK and SUR1 mRNA expression. We also examined whether caudal hindbrain lactate repletion alters the impact of hypoglycemia on substrate fuel uptake and metabolic sensing functions in other characterized metabolic monitoring sites, e.g., the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA). qPCR was used to measure MCT2, GLUT3, GLUT4, GK, and SUR1 transcripts in the microdissected DVC, VMH, and LHA from groups of male rats treated by continuous infusion of aCSF or lactate into the caudal fourth ventricle (CV4), initiated prior to injection of Humulin R or saline. Blood glucose was decreased in response to insulin, a response that was significantly augmented by CV4 lactate infusion. IIH alone did not alter mean DVC MCT2, GLUT3, GLUT4, GK, or SUR1 mRNA levels, but these transcripts were increased in the lactate plus insulin group, relative to both euglycemic and aCSF-infused hypoglycemic rats. IIH decreased MCT2, GLUT3, and SUR1 gene profiles in the VMH; CV4 lactate infusion during IIH further diminished these transcripts, and suppressed GLUT4 and GK mRNA levels in this site. In LHA, IIH increased GLUT3 and SUR1 gene expression to an equal extent, with or without lactate, while GLUT4, MCT2, and GK mRNA levels were elevated only in response to lactate plus insulin. These studies show that caudal hindbrain-targeted delivery of exogenous lactate during IIH upregulates neuronal monocarboxylate and glucose transporter, GK, and SUR1 gene profiles in the DVC, and results in increased or decreased GLUT4 and GK mRNA in LHA and VMH, respectively. These data suggest that lactate and glucose utilization by DVC neurons may be enhanced in response to local lactate surfeit, alone or relative to glucose deficiency, and that increases in intracellular glucose and net energy yield may be correlated with elevated GK and SUR1 gene transcription, respectively, in local glucose sensing neurons. The results also imply that GLUT4- and GK-mediated glucose uptake and glucose sensing functions in the VMH and LHA may be reactive to DVC signaling of relative lactate abundance within the caudal hindbrain, and/or to physiological sequelae of this fuel augmentation, including amplified hypoglycemia.

Ingestive effects of NMDA and AMPA-kainate receptor antagonists microinjections into the lateral hypothalamus of the pigeon (Columba livia).

This study examined the ingestive and behavioral effects of NMDA- and AMPA/kainate glutamatergic receptor blockade in the lateral hypothalamic area (LHy) of free-feeding pigeons (Columba livia). Injections of MK-801 (NMDA receptor antagonist; 6 nmol) or CNQX (AMPA/kainate receptor antagonist; 25.8 nmol) into the LHy of free-feeding pigeons induced significant increases in food intake and in feeding duration, as well as reductions in the latency to start feeding. Duration, latency and volume of water intake, as well as duration of sleep-like behavior, alert immobility, locomotion and preening were not changed by these treatments in the LHy. These results indicate that glutamatergic inputs to cells containing NMDA and/or AMPA receptors located in the LHy could modify both the beginning of a feeding bout (or the end of a period of satiety) and its duration (satiation). Our data also suggest that these inhibitory glutamatergic influences on feeding behavior are tonically active in the LHy.

Sleep-active neurons in the preoptic area project to the hypothalamic paraventricular nucleus and perifornical lateral hypothalamus.

The lamina terminalis consists of the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ. The MnPO and ventrolateral preoptic area (vlPOA) are known to contain high densities of neurons that are sleep active. The prevalence of sleep-active neurons in the OVLT and subfornical organ is unknown. The vlPOA and subdivisions of the lamina terminalis project to hypothalamic regions involved in the control of behavioral, electrographic or autonomic arousal, including the lateral hypothalamic area (LHA) and paraventricular nucleus (PVN). The extent to which projection neurons are active during sleep is unknown. We quantified c-Fos protein immunoreactivity (IR) in the lamina terminalis and vlPOA in sleeping and awake rats that received injections of retrograde tracer into either the LHA or PVN. Fos IR was also examined in lamina terminalis neurons following tracer injections into the vlPOA. Significantly more projection neurons from the MnPO, OVLT and vlPOA to the LHA were Fos-immunoreactive in sleeping vs. awake animals. Waking Fos IR was more prevalent in lamina terminalis neurons projecting to the PVN although a subset of MnPO projection neurons in sleeping rats was Fos-immunoreactive. Almost 50% of vlPOA-PVN projection neurons expressed Fos IR during sleep, compared with 3% during waking. Significantly more neurons in the OVLT and MnPO projecting to the vlPOA were Fos-immunoreactive in sleeping vs. awake rats. Inhibition of LHA and PVN neurons arising from OVLT, MnPO and vlPOA neurons may contribute to suppression of behavioral, electroencephalographic and sympathetic nervous system activation during sleep.

Lesions of tuberomammillary nuclei induce differential polydipsic and hyperphagic effects.

This study aimed to examine the function of the tuberomammillary complex in water and food intake of Wistar rats. The results show that lesions restricted to tuberomammillary subnuclei: caudal ventral tuberomammillary nucleus (E1), rostral ventral tuberomammillary nucleus (E2), medial ventral tuberomammillary nucleus (E3) or medial dorsal tuberomammillary nucleus (E4), induce a strong and persistent polydipsia with specific characteristics for each nucleus. Interestingly, the distribution of tuberomammillary hyperdipsia throughout the day was similar to that in non-lesioned animals, in contrast to the lack of rhythmicity observed in rats with anodic lesion to median eminence. This polydipsia appears to be independent of food intake, as food deprivation for 22 h did not significantly reduce the water intake. Finally, lesions in ventral tuberomammillary nuclei E1 and E2 induce hyperphagia, confirming a possible role for the tuberomammillary complex in food intake. This increase in food intake is not observed after lesions in medial subnuclei E3 and E4. These results are interpreted in terms of the hypothalamic systems involved in the consumption of both food and water.