Lateral Habenula

Exposure to short photoperiod induced a major reduction in the expression of vasopressin in BNST neurons, as well as in their target areas, the lateral septum (LS) and the lateral habenula (LHb).  

The lateral habenula (HbL) receives noxious inputs and has an inhibitory influence on the nigral dopaminergic neurons.  

We recently showed evidence that the lateral habenula transmits reward-related signals to dopamine neurons, especially to inhibit dopamine neurons. This recent study suggested that the lateral habenula suppresses less rewarding saccadic eye movements by inhibiting dopamine neurons. In the present review, we first summarize anatomical and functional aspects of the lateral habenula. Finally, we will discuss how the lateral habenula, as well as dopamine neurons, contributes to the reward-based control of saccadic eye movements..  

This enhancement of the indirect mechanism may be caused by a punishment-predictive signal which originates from the lateral habenula and is mediated by dopamine neurons..  

Five potential targets have been identified in the literature: ventral striatum/nucleus accumbens, subgenual cingulate cortex (area 25), inferior thalamic peduncle, rostral cingulate cortex (area 24a), and lateral habenula.  

Recently obtained evidence points to the involvement of the lateral habenular nuclei (LHb) in the mediation of coping defensive responses to threatening/stressful stimuli.  

While all four SSRIs similarly reduced rCMRglc in a network of subcortical brain regions including the amygdala, locus coeruleus, basal ganglia and hypothalamic paraventricular nuclei, fluvoxamine, paroxetine and sertraline reduced rCMRglc also in the hippocampus and sertraline in the lateral habenula.  

Our findings here, however, indicate that this increase may involve active removal of a tonic inhibitory control on dopamine neurons exerted by the lateral habenula (LHb).  

Litter presence before testing affected Fos expression due to handling or elevated plus-maze exposure only in the ventral bed nucleus of the stria terminalis, dorsal and ventral preoptic area, ventromedial hypothalamus, lateral habenula, and supramammillary nucleus.  

We investigated the effects of lateral habenular nucleus (LHb) lesions on the behavioral response and on the level of 5-HT in DRN in the depressed rats.  

Recent studies suggesting that the lateral habenula (LHb) may contribute to this type of signaling in humans prompted us to evaluate the effects of LHb stimulation on the activity of dopamine and non-dopamine neurons of the anesthetized rat.  

Thus, in addition to the SCN, a number of areas of the mammalian brain including the olfactory bulb, amygdala, lateral habenula and a variety of nuclei in the hypothalamus, express circadian rhythms in core clock gene expression, hormone output and electrical activity.  

Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons..  

Increased activation of the lateral habenular nucleus leads to the down regulation of the serotonergic, noradrenergic, dopaminergic systems and stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. Functional inhibition of the lateral habenula via deep brain stimulation (DBS) has antidepressive properties.  

The lateral habenula is the principal actor in this direct dialogue, while the medial habenula mostly conveys information to the interpeduncular nucleus before this modulates further regions.  

Fos-positive neurons were counted in a 0.3-mm(2) area from 5 regions previously shown to express T-induced Fos: the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), ventral tegmental area, and lateral pontine nucleus.  

The RLi also sends substantial projections to the magnocellular preoptic nucleus, lateral hypothalamus, central division of the mediodorsal thalamic nucleus, lateral part of the lateral habenula and supraoculomotor region, and light projections to the prefrontal cortex, basolateral amygdala, and dorsal raphe nucleus. Overall, the data suggest that the RLi is a distinct VTA component in that it projects primarily to pallidal regions of the olfactory tubercle and to their diencephalic targets, the central division of the mediodorsal thalamic nucleus and the lateral part of the lateral habenula.  

Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets.  

Previous anatomical and physiological studies have implicated the lateral habenula, and especially its medial division (LHbM), as a candidate component of the circadian timing system in rodents. We assayed lateral habenula rhythmicity in rodents using c-FOS immunohistochemistry and found a robust rhythm in immunoreactive cell counts in the LHbM, with higher counts during the dark phase of a light-dark (LD) cycle and during subjective night in constant darkness. Locomotor activity rhythms appear to be regulated by the suprachiasmatic nucleus (SCN) via multiple output pathways, one of which might be diffusible while the other might be neural, involving the lateral habenula..  

None of these was associated with substantial ipsilateral loss of NT-ir in the VTA, lateral hypothalamus or lateral habenula.  

A similar trend was observed in other areas such as the lateral habenula, somatosensory cortex and hippocampal regions (percentage changes of 27-41%), but these did not reach significance.  

We found that progesterone decreased AVP-ir labelling within the BST and CMA, as well as in two of the projection sites of these cells, the lateral septum and lateral habenula.  

They fall into eight general categories: humeral sensory-related (subfornical organ and median preoptic nucleus, involved in initiating drinking behavior and salt appetite), neuroendocrine system (magnocellular: oxytocin, vasopressin; parvicellular: gonadotropin-releasing hormone, somatostatin, thyrotropin-releasing hormone, corticotropin-releasing hormone), central autonomic control network (central amygdalar nucleus, BST anterolateral group, descending paraventricular hypothalamic nucleus, retrochiasmatic area, ventrolateral periaqueductal gray, Barrington's nucleus), hypothalamic visceromotor pattern-generator network (five of six known components), behavior control column (ingestive: descending paraventricular nucleus; reproductive: lateral medial preoptic nucleus; defensive: anterior hypothalamic nucleus; foraging: ventral tegmental area, along with interconnected nucleus accumbens and substantia innominata), orofacial motor control (retrorubral area), thalamocortical feedback loops (paraventricular, central medial, intermediodorsal, and medial mediodorsal nuclei; nucleus reuniens), and behavioral state control (subparaventricular zone, ventrolateral preoptic nucleus, tuberomammillary nucleus, supramammillary nucleus, lateral habenula, and raphé nuclei).  

Outside the SCN, visual inspection revealed an obvious left-right asymmetry of c-Fos expression in the medial preoptic nucleus and subparaventricular zone of split hamsters killed during the inactive phase and in the medial division of the lateral habenula during the active phase (when the hamsters were running in their wheels). Roles for the dorsolateral SCN and the mediolateral habenula in circadian timekeeping are not yet understood..  

The former include inputs to anterior hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and ventral region of the dorsal premammillary nucleus (defensive behavior control system components), and to lateral habenula and dorsal region of the dorsal premammillary nucleus (foraging behavior control system components).  

Testosterone infusion induced Fos above control in the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), median raphe (MnR), lateral pontine nucleus (Pn), and ventral tegmental area (VTA).  

Third, about 10% of the cells in the lateral habenula showed a strong correlation between rate and angular head motion.  

Expression of c-Fos was examined in the lateral habenula (LHb), a region important for conveying information between the limbic forebrain and midbrain.  

Org 24448 (3 mg/kg) produced significant increases in LCGU in 4 of the 43 regions examined, including the dorsal raphe nucleus, medial lateral habenula, CA1 subfield of the hippocampus and median forebrain bundle.  

However, there are also differences in the expression patterns, for example, high expression of MCHR1 was detected in the lateral habenula, but no expression of MIZIP.  

As a step to improve our understanding of how information delivered from the limbic forebrain and pallidum is processed in the habenula, we examined the electrical property and morphology of medial and lateral habenular cells. Medial habenular cells generate tonic trains of action potentials, whereas lateral habenular cells are capable of producing action potentials in burst mode. lateral habenular cells produce dendrites that are much longer than those of medial habenular cells. Two distinct intrinsic circuits exist in the medial habenular nucleus, whereas in the lateral habenular nucleus, intrinsic axons travel largely from medial to lateral direction. The connection between the two habenular nuclei is asymmetrical in that only the medial habenula sends projection to the lateral habenula. The differences in the electrical and morphological properties of medial and lateral habenular cells indicate that the two nuclei process and integrate information in distinct fashions that is delivered from the limbic forebrain and pallidum..  

The sexually dimorphic extrahypothalamic arginine-vasopressin (AVP) projections from the bed nucleus of the stria terminalis to the lateral septum (LS) and lateral habenula (LHb) are denser in males than females and, in rats, require males' perinatal exposure to gonadal hormones but the absence of such exposure in females.  

LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus.  

A significant increase of Fos immunoreactive cells were observed in the solitary tract nucleus, locus ceruleus, lateral parabrachial nucleus, ventrolateral part of central gray, medial amygdaloid nucleus, central amygdaloid nucleus, ventromedial part of thalamus, dorsomedial part of thalamus, hypothalamic paraventricular nucleus, lateral habenula, and lateral septum nucleus following SEB challenge.  

central amygdala, lateral habenula, dorsomedial caudate putamen) or sensitized (e.g. medial nucleus accumbens core, central amygdala, lateral habenula) methamphetamine treatment were identified, thereby providing a comprehensive map of the short and long-term effects of methamphetamine on mouse brain activity per se.  

The spatial expression of the Php protein was in the neuronal fibers of the medial part of lateral habenula nucleus, thalamus, hypothalamus, stria terminalis, zona incerta, amygdaloid body and cingulum, olfactory bulb, hippocampus, cerebral cortex and cerebellum.  

Histological analysis showed that habenula lesions substantially damaged both medial and lateral habenula bilaterally while largely sparing neighbouring structures.  

By using extracellular and intracellular recordings in slice preparations, we demonstrate that the activation of synaptic input from the limbic forebrain generates transient hyperpolarizing postsynaptic potentials in neurons of the medial part of the lateral habenular nucleus of the epithalamus. The cells in the medial division of the lateral habenula project to dopamine and serotonin cells in the midbrain.  

This effect was region-specific and was greatest in caudate putamen, nucleus accumbens, bed nucleus stria terminalis and lateral habenula, and lacking in other areas including cingulate and insular cortices, lateral septum and central amygdaloid nucleus.  

In cases with spinal lamina I injections, terminations were also consistently found in the lateral habenula, the parafascicular nucleus, and the nucleus reuniens. The novel identification of spinal lamina I input to the lateral habenula could be significant for homeostatic behaviors..  

An anxiogenic or a pharmacological stressor, N-methyl-beta-carboline-3-carboxamide (FG-7142), (20 mg/kg, intraperitoneally injected) induced a dense nuclear c-Fos-like immunoreactivity in the pyriform cortex, cingulate and retrosplenial cortex, layers II-VI of the neocortex, lateral habenula, lateral septum, paraventricular nucleus of the thalamus, striatum, central and medial nucleus of the amygdala, but a sparse c-Fos immunostaining in the hippocampus and layer I of the neocortex in the forebrain of 56-day-old rats. Among these regions, the 8-day-old rats expressed much fewer c-Fos-positive cells in the neocortex, lateral habenula, lateral septum and medial nucleus of the amygdala than the young adult rats following the FG-7142 injection.  

In the present study, anterograde tracer injections in the nucleus incertus resulted in terminal-like labeling in the perirhinal cortex and the dorsal endopyriform nucleus, the hippocampus, the medial septum diagonal band complex, lateral and triangular septum medial amygdala, the intralaminar thalamic nuclei, and the lateral habenula. These data led us to conclude that there is a system of ascending projections arising from the nucleus incertus to the median raphe, mammillary complex, hypothalamus, lateral habenula, nucleus reuniens, amygdala, entorhinal cortex, medial septum, and hippocampus.  

Moreover, the systemic effect of clonidine on 5-HT (but not NA) was cancelled by lesion of the lateral habenula and by anesthesia, and was slightly enhanced by cortical transection.  

5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice.  

In quinpirole-naive rats, quinpirole decreased LCGU in the caudate/putamen (84% of control), lateral habenula (80% of control), and motor cortex (79% of control). In sensitized rats, quinpirole decreased LCGU in the nucleus accumbens core and shell (77 and 83% of control, respectively) and ventral pallidum (82% of control) as well as in the caudate/putamen (86% of control), lateral habenula (77% of control), and motor cortex (79% of control).  

Neuronal projections to the dorsal raphe nucleus (DRN) from the medial prefrontal cortex (mPFC) and lateral habenula nucleus (LHb) provide the two key routes by which information processed by mood regulatory, cortico-limbic-striatal circuits input into the 5-HT system.  

By standard t tests, the high dose statistically significantly lowered baseline CBF in frontal and visual cortex, hippocampus, dentate gyrus, inferior olive, cerebellar cortex, and the ventral posteromedial (VPM) thalamic nucleus on the unstimulated side, and raised baseline CBF in the lateral habenula; however, these changes lost statistical significance after Bonferroni correction for multiple comparisons.  

Regions in which there were significant changes in the conditioned group included the basolateral amygdala, subiculum, medial thalamus, lateral habenula and the substantia nigra pars compacta.  

In vitro electrophysiological investigation showed that these effects were not mediated by a direct action in the DRN, an observation supported by immunocytochemical analysis that identified the lateral habenula (LHb) as a more likely site of action.  

A variety of drugs which predominantly potentiate dopamine, including D-amphetamine, methamphetamine, MDMA, cocaine, and cathinone, all induce degeneration in axons from lateral habenula, through the sheath of FR, to midbrain cells such as SN, VTA, and raphe.  

The amygdala, in particular, is not engaged after retrieval, whereas the lateral habenula (LHab) shows strong activation that is restricted to animals having previously learned the association.  

Retrogradely radiolabelled neurons in various numbers were detected in several brain regions including medial septum-diagonal band complex, lateral septum, rostral part of medial and lateral preoptic areas, lateral habenula, ventral premammillary nucleus, apical subregion of interpeduncular nucleus, laterodorsal tegmental nucleus, and dorsal and median raphe nuclei.  

Metabolic differences between trained aged and young rats were found in regions related to escape under stress: perirhinal cortex, basolateral amygdala and lateral habenula; and vestibular nuclei that guide orientation in three-dimensional space.  

Likewise, 300 microM CP-93,129 reduced 5-HT output in substantia nigra pars reticulata, ventral pallidum, lateral habenula and the suprachiasmatic nucleus.  

Only GAL-ir fibers were seen in the lateral habenula nucleus, substantia nigra, parabrachial complex, cerebellum, spinal trigeminal tract, as well as the motor root of the trigeminal and facial nerves.  

Following intragastric HCl (0.5 M) challenge, many neurons in the nucleus tractus solitarii, lateral parabrachial nucleus, thalamic and hypothalamic paraventricular nucleus, supraoptic nucleus, central amygdala and medial/lateral habenula expressed c-fos mRNA as compared to intragastric treatment with saline (0.15 M).  

In addition, moderately stained zinc-rich terminal fields were found in the rostral intralaminar nuclei, nucleus reuniens and lateral habenula.  

When administered continuously for several days at relatively low plasma levels, a variety of drugs of abuse with strong dopaminergic actions induce degeneration in axons traveling from the lateral habenula through the sheath of fasciculus retroflexus to midbrain monoaminergic nuclei.  

The entopeduncular nucleus (EP) is a major outflow nucleus of the basal ganglia and innervates the lateral habenula, parafascicular, pedunculopontine, ventrolateral (VL), ventromedial (VM), and mediodorsal thalamic nuclei. This excitatory input is most likely derived from axons that branch as they pass through the motor thalamus to the lateral habenula..  

On the other hand, pentobarbital by itself strongly induced c-Fos expression in the lateral habenula of saline-, cocaine-, and ethanol-injected rats. It is not clear whether the suppressive effects of anesthesia on ITF expression in other areas are mediated by activation of lateral habenula, or are independent of this event.  

As expected, the number of ERalpha-immunoreactive (ERalpha-ir) neurons did not differ between the two groups in the eight areas analyzed (lateral region of the lateral septum, posterodorsal medial amygdala, dorsal and ventral medial preoptic area, dorsal and ventral bed nucleus of the stria terminalis, lateral habenula, and ventrolateral caudal periaqueductal gray). Maternal dams had significantly more Fos-ir neurons that also contained ERalpha-ir in all sites, with the greatest increases in the ventral medial preoptic area, lateral habenula, and ventral bed nucleus of the stria terminalis.  

GK also was found in brain areas without known glucosensing neurons (the lateral habenula, the bed nucleus stria terminalis, the inferior olive, the retrochiasmatic and medial preoptic areas, and the thalamic posterior paraventricular, interpeduncular, oculomotor, and anterior olfactory nuclei).  

Paired rats also showed increased FRA expression within the orbital prefrontal cortex, the claustrum, the caudal amygdala (basolateral and central regions), the paraventricular thalamic nucleus, the subiculum of the hippocampus, and the lateral habenula relative to the Control group.  

Similar results were observed in the ventral subiculum of the hippocampus and the basolateral and central amygdaloid nuclei, but not in the lateral septum or lateral habenula.  

In the rat, we observed VR1-expressing neurons throughout the whole neuroaxis, including all cortical areas (in layers 3 and 5), several members of the limbic system (e.g., hippocampus, central amygdala, and both medial and lateral habenula), striatum, hypothalamus, centromedian and paraventricular thalamic nuclei, substantia nigra, reticular formation, locus coeruleus, cerebellum, and inferior olive.  

All other sites showed evidence of excitatory input-output relationships (i.e., joint increase in both 2-DG and c-fos activity), e.g., bed nucleus of the stria terminalis (BNST), lateral habenula (LHAB), central gray (CG), thalamus (THAL), septum (SEPT), and ventral tegmental area (VTA).  

Chlorisondamine significantly reduced LCGU in the lateral habenula, substantia nigra pars compacta, ventral tegmental area, and cerebellar granular layer.  

Regional effects were restricted to parietal and retrosplenial cortices, lateral habenula and the basal forebrain.  

The lateral habenula is a nucleus in the dorsal thalamus that innervates midbrain dopaminergic and serotonergic nuclei via projections through its major efferent pathway, the fasciculus retroflexus (FR). It was previously demonstrated that cocaine administered continuously to adult rats over several days produces neurodegeneration in the lateral habenula and FR. Because exposure to cocaine during pregnancy reportedly can cause neurobehavioral deficits, we examined whether rat fetuses exposed to continuous cocaine during the last week of gestation would similarly demonstrate selective neurodegeneration in the lateral habenula. Degenerating neurons containing silver deposits were counted in lateral habenula and in the striatum. Cocaine-exposed pups had significantly more silver-stained cells in the lateral habenula than vehicle-treated pups, but similar numbers of silver-stained cells were present in the striatum of all three groups.  

C-ret mRNA was abundant in areas such as the lateral habenula, reticular thalamic nucleus, substantia nigra pars compacta, cranial motor nuclei, and the Purkinje cell layer of the cerebellum.  

The lateral habenula (LH) was the only area in which both maternal juveniles and maternal adults had more c-Fos-immunoreactive (-Ir) neurons compared with controls.  

The relation of these results to persisting alterations in mesocorticolimbic pathways and previous findings of cocaine-induced degeneration in lateral habenula circuitry is discussed..  

significant increases in the corpus callosum, olfactory tubercle and the entire Papez circuit, in addition to other limbic areas, and significant decreases in lateral habenula and some components of the auditory system).  

AVP-immunoreactive (AVP-ir) fibre density in the lateral septum (LS) and lateral habenula (LHb), expressed by the number of pixels that covered AVP-ir fibres during computerized optical density analysis, was greater in males than females, was non-significantly reduced in castrated males, and doubled in the LS of oestradiol-treated females.  

In contrast, the centrolateral thalamic nucleus and lateral habenula have little serotonergic innervation, but receive substantial other neural input from the raphe nuclei.  

MR fibers distribute densely to the following brainstem/forebrain sites: caudal raphe nuclei, laterodorsal tegmental nucleus, dorsal raphe nucleus, interpeduncular nucleus, medial mammillary body, supramammillary nucleus, posterior nucleus and perifornical region of the hypothalamus, midline and intralaminar nuclei of thalamus, dopamine-containing cell region of medial zona incerta, lateral habenula, horizontal and vertical limbs of the diagonal band nuclei, medial septum, and hippocampal formation.  

We demonstrated previously that the lateral habenula (Lhb) mediates maternal behavior.  

The lateral habenula (Lhb), which is a necessary component in the neural circuit that supports maternal behavior, contains a subset of neurons with estrogen receptors.  

GLP-1R mRNA was detected in numerous brain regions, including the mitral cell layer of the olfactory bulb; temporal cortex; caudal hippocampus; lateral septum; amygdala; nucleus accumbens; ventral pallium; nucleus basalis Meynert; bed nucleus of the stria terminalis; preoptic area; paraventricular, supraoptic, arcuate, and dorsomedial nuclei of the hypothalamus; lateral habenula; zona incerta; substantia innominata; posterior thalamic nuclei; ventral tegmental area; dorsal tegmental, posterodorsal tegmental, and interpeduncular nuclei; substantia nigra, central gray; raphe nuclei; parabrachial nuclei; locus ceruleus, nucleus of the solitary tract; area postrema; dorsal nucleus of the vagus; lateral reticular nucleus; and spinal cord.  

In the thalamus, novel sites of expression included the anterodorsal nucleus, lateral habenula, and zona incerta, where labeling was much more extensive than previously reported.  

Infusion of quinolinic acid into the MD using a glass micropipette produced well-defined neuronal loss restricted to medial and lateral portions of the MD, sparing adjacent areas such as the lateral habenula and paraventricular thalamic nucleus.  

The latter two nuclei projected to the lateral habenula and, at least the nucleus of the posterior pallial commissure, to the mammillary complex.  

l-Nafadotride produced significant increases in LCGU in several brain areas including the lateral preoptic area, lateral habenula, caudate, septal area, entorhinal cortex, and some thalamic and hypothalamic areas.  

We previously reported that subchronic administration of cocaine for 5 days via slow-release pellets results in pronounced degeneration in the lateral habenula (LHB) and its primary efferent tract, the fasciculus retroflexus [ Ellison (1992): Brain Res 598:353-356; Ellison and Switzer (1993): Neuroreport 5:17-20]. The lateral habenula receives both GABA and glutamate afferents.  

Test day treatment with U-50,488 stimulated Fos IR in various brain regions of the preweanling rat, including the medial striatum, nucleus accumbens, lateral habenula, and septal area.  

Moderate increases were observed in the entorhinal cortex, lateral septum, lateral habenula, lateral amygdaloid nucleus, dentate gyrus, and mesencephalic central grey.  

Evidence is presented for the ideas that primary delusions are due to memories of dream events, that a substance, with vasotocin-like bioactivity, is released in the brain during dreaming and inhibits memory formation, that the lateral habenula is a brain area involved in vasotocin actions and is affected by neuroleptics, and that brain mechanisms involved in vasotocin actions show pathological alterations in schizophrenia..  

The binding was almost exclusively localised to the medial and lateral habenula, interpeduncular nucleus and pineal gland; at 0.1 nM 3[ H]epibatidine it represented about 40% of the total 3[ H]epibatidine binding.  

c-Fos was preferentially induced in terminal fields of neurons of the ventral tegmental area such as the nucleus accumbens, the central amygdala, the lateral habenula, the lateral septum, as well as the cingulate, medial prefrontal, orbital and piriform cortices.  

No positive Ggama3 immunoreactivity was observed in the lateral habenula, lateral septal nucleus, or Purkinje cells.  

Since the majority of glutamatergic afferents to the median raphe nucleus originates from the lateral habenula and the interpeduncular nucleus, known to connect limbic forebrain to the brainstem, theta associated changes in median raphe nucleus glutamate levels might reflect descending forebrain influences, suggesting therefore a feedback regulation of the hippocampal activity involving brainstem structures..  

Neurons within the lateral habenula (LHb), but not the medial habenula, express ER mRNA, contain ER immunoreactivity (ER-ir) in their nuclei, and concentrate radiolabelled estradiol, providing strong evidence for the presence of functional ER in the lateral habenula.  

Brain regions in which amphetamine increased c-Fos-like immunoreactivity, but modafinil had no effect, included frontal cortex, striatum, lateral habenula, supraoptic nucleus and basolateral nucleus of the amygdala.  

Physical interaction with pups, with or without suckling, elicited higher levels of Fos-immunoreactive nuclei than that of other conditions in numerous sites, including many previously implicated in maternal behaviour (medial preoptic nucleus, nucleus accumbens, lateral septum, lateral habenula, and the bed nucleus of the stria terminalis).  

In agreement with previous studies, we observed a large number of retrogradely-labelled cells in the lateral habenula following injections in all subdivisions of the dorsal raphe nucleus.  

The areas with the highest Fos-like immunoreactivity were ipsilateral to the electrode site and included the medial prefrontal cortex, lateral septum, nucleus accumbens (shell), the medial and lateral preoptic areas, bed nucleus of the stria terminalis, central amygdala, lateral habenula, dorsomedial hypothalamus, lateral hypothalamus and the anterior ventral tegmental area.  

In PD1 rats, ER-alpha-immunoreactive (ER-IR) signals were detected in the lateral septum, the organum vasculosum lamina terminalis, the medial preoptic nucleus (MPN), the median preoptic nucleus, the bed nucleus of the stria terminalis, the hypothalamic periventricular nucleus, the lateral habenula, the posterodorsal part of the medial amygdala nucleus, the posterior part of the cortical amygdala nucleus, the hypothalamic ventromedial nucleus (VMH), the hypothalamic arcuate nucleus, and the posterior hypothalamic periventricular nucleus.  

Perikarya in other brain regions, including the bed nucleus of the stria terminalis, medial and cortical amygdaloid nuclei, preoptic area, lateral habenula, periaqueductal gray, parabrachial nucleus, locus ceruleus, nucleus of the solitary tract, spinal trigeminal nucleus and superficial laminae of the spinal cord, contained both forms of ER mRNA.  

Labeled fibers and terminals were also observed in the avian subthalamic nucleus and the inmediately adjacent lateral hypothalamus, the avian thalamic reticular nucleus, the avian medidorsal nucleusaand posterior intralaminar nuclei, and the lateral habenula.  

As measured by Fos immunohistochemistry, the AMPH sensitization procedure enhanced subsequent AMPH-induced Fos expression in only one structure, the medial part of the lateral habenula. The lateral habenula appears to be involved in the possible neural framework that is responsible for the expression of behavioral sensitization..  

Compared to the control group, post-partum animals and animals that had received VCS showed increased c-fos expression in a number of cortical regions (cingulate, entorhinal and somatosensory), the mediodorsal thalamic nucleus and the lateral habenula, the limbic system (bed nucleus of the stria terminalis, lateral septum, medial arnygdala, dentate gyrus and the CA3 region of the hippocampus) and the hypothalamus (medial preoptic area, mediobasal hypothalamus, paraventricular nucleus, supraoptic nucleus and periventricular complex).  

CA3 pyramidal cell layer, intramediodorsal thalamic nucleus and lateral habenula displayed a high mRNA expression at PN5 and PN8 which decreased throughout development but it was still present in adults.  

On Day 5, WGA was iontophoretically injected into one of the following regions known to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the level of the ventromedial nucleus, lateral habenula, ventral tegmental area, retrorubral field, or periaqueductal gray.  

Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches.  

Aromatase-immunoreactivity was present in neuronal perikarya and axonal processes in the following limbic structures: the central and medial nuclei of the amygdala, stria terminalis, bed nucleus of the stria terminalis (BNST), lateral septum, medial septum, diagonal band of Broca, lateral habenula and all areas of the limbic (cingulate) cortex.  

We have previously shown that systemic administration of non-selective dopamine agonists results in a pronounced expression of the proto-oncoprotein Fos within the lateral habenula. The selective agonists, by themselves, induced only small increases in Fos-like immunoreactivity within the lateral habenula, but combinations of the two drugs resulted in a very robust response.  

The second group included nuclei showing scattered, moderately labeled cells; these areas were widespread at all rostrocaudal levels and related to either autonomic/neuroendocrine regulations (central gray, lateral habenula, hypothalamus) or motor behavior, orienting reflex and oculomotor coordination (unspecific subdivisions of both colliculi and their adjoining mesencephalic regions, zona incerta dorsal).  

In the lateral habenula specific binding declined by only 30-40%, reflecting the presence of a 5-HT pathway deviating from the MFB at the mesencephalic flexure.  

The study has shown an excitatory influence exerted by lateral habenula (LH) on hippocampal pyramidal cells.  

Moreover, females show higher brain glucose utilization in all regions examined, including sex hormone-responsive regions such as the medial amygdala, medial preoptic nucleus, ventromedial nucleus, and arcuate nucleus, as well as the CA1 layer and dentate region of the hippocampus, the posterior parietal (sensorimotor) cortex, medial and lateral habenula, and splenium of the corpus callosum.  

In addition, glycine-immunoreactive cells were seen in the ambiguous and subtrigeminal nuclei, the lateral habenula and the subfornical organ.  

The two statistically significant changes common to food-restricted and diabetic rats are increased kappa binding in the medial preoptic area and decreased mu binding in the lateral habenula.  

In 3-month-old rats, MFT (80 mg/kg i.p.) increased LCGU significantly in 17 of the 54 regions studied, including insular, cingulate, and temporal cortices, ventral hippocampus, thalamus, lateral habenula, substantia nigra, and superior colliculus.  

However, in response to mild stress several brain regions, particularly the lateral habenula (LHb), exhibited differences in c-fos induction in dtsz hamsters and controls. Since the lateral habenula receives major input from the basal ganglia via the entopeduncular nucleus, the present data might indicate that basal ganglia are involved in the dystonic syndrome in mutant hamsters..  

Levodopa infusion at 100 mg/kg/day resulted in minimal rotation and minimal striatal dopamine replacement but did increase RCGU in the subthalamic nucleus and decrease RCGU in the lateral habenula, consistent with a selective inhibition of the striatopallidal GABAergic (indirect striatal output) pathway.  

Using simultaneous extracellular single-unit recording in the pars compacta of the substantia nigra and in the lateral habenula of rats, 45 pairs of neurons responding to peripheral nociceptive stimulation were recorded. In 41 of these pairs, nigral dopaminergic neurons were inhibited by peripheral nociceptive stimulation, while lateral habenula neurons were excited. Moreover, in 14 pairs, when sweeps were triggered randomly by spontaneous spikes from lateral habenula neurons the spontaneous firing rate of the dopaminergic neurons during the first 250 ms after the sweep was much lower than rates after this time period. In this case, the sweep was often triggered by burst-firing of lateral habenula neurons. Our results indicate a cross-correlation between the spontaneous activities of these two nuclei, suggesting that the excitation of lateral habenula neurons induced by peripheral nociceptive stimulation might be directly responsible for inhibition of nigral dopaminergic neurons..  

This results in a 100-fold increase in AVP mRNA in the BNST and a massive increase in AVP peptide in the BNST and its projections to the lateral septum and lateral habenula.  

Signal was also identified in the medial and lateral habenula, in the central, medial, basomedial and anterior cortical nuclei of the amygdala, and in the CA1-CA3 and dentate gyrus of the hippocampus.  

Previously, we have demonstrated that lateral habenula (LH) modulates the bioelectric activity of the hippocampus through the dorsal raphe nucleus functional involvement.  

AVP concentrations in the lateral septum (LS) and the lateral habenula (LH), determined by radioimmunoassay, increased dose and time dependently.  

Fos-like immunoreactivity that was found in the vocalizing but not in the non-vocalizing animals was located in the dorsomedial and ventrolateral prefrontal cortex, anterior cingulate cortex, ventrolateral premotor cortex, sensorimotor face cortex, insula, inferior parietal cortex, superior temporal cortex, claustrum, entorhinal and parahippocampal cortex, basal amygdaloid nucleus, anterior and dorsomedial hypothalamus, nucleus reuniens, lateral habenula, Edinger-Westphal nucleus, ventral and dorsolateral midbrain tegmentum, nucleus cuneiformis, sagulum, pedunculopontine and laterodorsal tegmental nuclei, ventral raphe, periambigual reticular formation and solitary tract nucleus. lateral habenula, Edinger-Westphal nucleus), the available evidence speaks against such a role.  

In 16-day pregnant, hysterectomized-ovariectomized and estradiol benzoate-treated rats, cytotoxic lesions of the lateral habenula (Lhb) produced severe deficits in maternal behavior (K.P.  

Less marked effects occurred in the lateral habenula, dorsal raphe and substantia nigra pars compacta.  

THA (10 mg/kg i.p.) increased LCGU significantly in 13 of the 54 regions studied (24%) including insular, parietal, temporal, and retrosplenial cortices, septohippocampal system, thalamus, lateral habenula, and superior colliculus.  

Altered rates of glucose utilization were measured in extrapyramidal motor areas, such as the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra and lateral habenula of both cocaine- and apomorphine-treated rats.  

Dense iDAT was observed in patterns consistent with neural processes and terminals in the striatum, nucleus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula.  

The descending efferent connections of the sub-pallidal areas to the lateral habenula were investigated in the cat using Phaseolus vulgaris leucoagglutinin (PHA-L) as an anterograde tracer. Subsequently, the distribution of anterogradely labelled fibres in the lateral habenula was charted. PHA-L injections into the rostral part of the sub-pallidal regions resulted in a limited number of labelled fibres in the lateral habenula, while PHA-L injections into the caudal regions of the sub-pallidum resulted in an extensive distribution of anterogradely labelled fibres in this area. Thus, the lateral habenula is an important output structure of the sub-pallidal areas in the cat..  

High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone.  

In previous experimental studies, carried out on cats, we demonstrated that electrical stimulation of lateral habenula (LH) at 0.5-3.0 Hz or 5-20 Hz had a double effect (low frequency-excitation; high frequency-inhibition) on the spontaneous firing rate of single hippocampal neurones.  

Microinjections of WIN 55,212-2 (5 micrograms/0.5 microliter) into the medial septal area, lateral habenula, perihypothalamic area, arcuate nucleus, and ventrolateral periaqueductal gray did not significantly affect tail-flick latencies.  

In previous works we studied, on cats, the effects of lateral habenula (LH) stimulation on hippocampal units.  

The largest change in somatostatin gene expression after dopaminergic lesions is the increase in somatostatin mRNA level sin neurons of the internal pallidum and lateral hypothalamus projecting to the lateral habenula.  

Injections in the dorsomedial hypothalamic nucleus labeled neurons in the rostral and caudolateral poles of the dorsal cortex, anterior septal nucleus, horizontal limb of the diagonal band, nucleus of the anterior commissure, several hypothalamic areas, the lateral habenula, the posteroventral thalamic nucleus, and cells scattered around the dorsolateral anterior thalamic nuclei.  

However, in some of the regions examined, local cerebral glucose utilization was slightly reduced, the most pronounced decreases being measured in some extrapyramidal, sensorimotor and limbic areas (dentate gyrus, septum, lateral habenula, amygdala).  

Neurons originating in the medial and lateral habenula provide an extensive afferent input to the midbrain that could serve as a negative feedback circuit.  

Some fibers and boutons were also observed in the rhomboid, interanterodorsal, and mediodorsal nuclei, and others course through the stria medullaris to the lateral habenula.  

Significant reductions in mu binding were observed in caudal portions of the medial and lateral habenula, and the basolateral and basomedial nuclei of the amygdala.  

On gestational day 18, D1A dopamine receptor message was noted in the neural retina, anterior olfactory nucleus, the insular, prefrontal, frontal, cingulate, parietal and retrosplenial cortices, the olfactory tubercle, caudate-putamen, lateral habenula, dorsolateral geniculate nucleus, ventrolateral and mediolateral thalamic nuclei, and the suprachiasmatic and ventromedial nuclei of the hypothalamus.  

The neurons projecting to the cerebellar cortex often issued axon collaterals to the cerebral cortical areas, including the prelimbic-anterior cingulate cortices and piriform-entorhinal cortices, but not so frequently to the subcortical regions, including the nucleus accumbens, lateral septum, amygdala, and lateral habenula.  

However, it has recently been found that both continuous amphetamine and cocaine induce a strong pattern of degeneration which is highly confined to the lateral habenula and its principal output pathway, fasciculus retroflexus.  

However, very high levels were also seen in many other brain regions, as the retrosplenial, piriform and entorhinal cortex, anterior olfactory nucleus, lateral septal nucleus, subthalamic nucleus, amygdala, subiculum and ventral part of CA3, lateral habenula, substantia nigra pars compacta, several brainstem nuclei and the whole grey matter of the spinal cord.  

Levodopa also decreased metabolic rate in lateral habenula (down 39%), a target of projections from entopeduncular nucleus, implying a reduction in basal ganglia output. Pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline reduced the effect of levodopa in substantia nigra pars reticulata but not in entopeduncular nucleus or subthalamic nucleus, while MK-801 attenuated the effect of levodopa in all three of these structures; neither 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline nor MK-801 altered the effect of levodopa in lateral habenula.  

In rats treated systemically with either amphetamine, amfonelic acid or apomorphine, large numbers of cells displaying Fos-like immunoreactivity (FLI) could be seen in the lateral zone of the lateral habenula. In contrast, a variety of stressors selectively induced FLI in the most medial portion of the lateral habenula. These findings support the concept of a functional differentiation of the medial and lateral regions of the lateral habenula and provide further evidence for involvement of the habenula in the circuitry of the basal ganglia..  

Diencephalic targets of ventral pallidal fibers are the lateral hypothalamus, the reticular nucleus of the thalamus, the mediodorsal thalamic nucleus, the dorsomedial part of the subthalamic nucleus, the medial part of the parafascicular nucleus and the lateral habenula.  

There were also patches of NADPH-d activity in the lateral habenula, but these did not match the AChE staining.  

Copulation with intromission and ejaculation in hormone-treated rats, or stimulation of the vaginal cervix in both hormone-treated and control rats, produced a dramatic induction of c-fos mRNA and Fos-like immunoreactivity in estrogen-concentrating regions, such as the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, ventromedial hypothalamus, lateral habenula, and medial amygdala, in addition to regions that do not readily concentrate estrogen, such as the neocortex, thalamus, and striatum.  

Limbic structures with significant metabolic increases included the lateral septum (48%), lateral habenula (44%), and nucleus accumbens (32%).  

LCGU increased in cortical areas (including parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolateral amygdala, the superior colliculus, and the substantia nigra.  

Linopirdine administered after hypoxia decreased glucose metabolism in the hippocampus, limbic cortex, ventral hippocampal commissure, medial septum, striatum, subthalamic nucleus, zona incerta, lateral habenula, cerebral cortex, cerebellar vermis and a few thalamic nuclei.  

The properties of the low-voltage-activated transient Ca2+ current (LVA, IT) that underlies rhythmic burst firing in neurons of the lateral habenula (LHb) were examined to further our understanding of mechanisms that promote rhythmogenesis in the CNS.  

SKF 38393 and quinpirole reduced 2-deoxyglucose uptake to a similar extent in the lateral habenula, a region which receives afferent input from entopeduncular nucleus; quinpirole also decreased glucose utilization bilaterally in nucleus accumbens. MK-801 did not alter the SKF 38393-induced reduction in glucose utilization in lateral habenula, but did reduce the effect of quinpirole in this structure. On the other hand, the preservation of D1-mediated rotational behavior and reduced lateral habenula glucose metabolism in the presence of MK-801 despite attenuation of the effects of the D1 agonist in entopeduncular nucleus and substantia nigra pars reticulata suggests that D1 receptor-regulated neuronal pathways exhibit varying degrees of sensitivity to N-methyl-D-aspartate receptor blockade..  

The fluorescent retrograde tracer fluorogold, or rhodamine-conjugated dextran, was injected into the lateral habenula or the ventrolateral nucleus of the thalamus of adult Wistar rats to identify the topographical organization of EPN-habenular and EPN-thalamic neurons.  

Administration of SCH 23390 increased RCGU in the lateral habenula, as do selective D2 antagonists. Systemic administration of amphetamine (5.0 mg/kg), a dopamine releasing agent, increased RCGU in the caudate-putamen (up 33%), globus pallidus (up 23%), subthalamic nucleus (up 46%), entopeduncular nucleus (up 78%), and SNr (up 72%) and lowered RCGU in the lateral habenula (down 43%).  

TSD rats showed tendencies for regionally specific increases in Egr-1-like immunoreactivity in dorsal raphe, lateral habenula, superior colliculus, and ventral periaqueductal grey.  

The unilateral 6-OHDA lesion per se (Sal-Sal) produced increases in lCMRglc in the globus pallidus (GP) and in the lateral habenula (LH) of the lesioned hemisphere.  

Other regions which receive sparse visual input include the lateral and anterior hypothalamic areas, the retrochiasmatic region, the sub-paraventricular zone, the paraventricular hypothalamic nucleus, the anteroventral and anterodorsal nuclei, the lateral habenula, the mediodorsal nucleus, and the basal telencephalon.(ABSTRACT TRUNCATED AT 400 WORDS).  

The critical damage was probably to the lateral habenula nucleus since it receives a major input from the LH.  

Single neurons in the lateral habenula of halothane-anesthetized cats were recorded extracellularly, and excitatory amino acid receptor agonists and antagonists were applied by iontophoresis. Most neurons in the lateral habenula were spontaneously active. Surprisingly, 116 (96%) out of 121 neurons in the lateral habenula responded to iontophoretic application of N-methyl-D-aspartate with a regular non-burst firing pattern, in contrast to previously published observations from other brain regions where N-methyl-D-aspartate predominantly elicited phasic firing patterns.  

In addition, the nigral lesion decreased glucose utilization in the dorso- and ventrolateral quadrants of the striatum and in the entopeduncular nucleus but increased glucose utilization in the ipsilateral globus pallidus and lateral habenula.  

Additional significant but much less marked increases in LCGU of rolling were found in some structures of the brainstem and limbic system, such as the pedunculopontine nucleus, red nucleus, ventral tegmental area, lateral habenula, and CA1 and CA3 of the hippocampus.  

Combined administration of MK-801 + SKF 38393 increased lCMRglc in the EP (+77%) and in the substantia nigra pars reticulata (SNr) (+30%) of the lesioned side as compared with the intact side, while it decreased lCMRglc in the lateral habenula (-26%).  

Consistent with its stimulant actions, cocaine produced an increase in locomotion that was accompanied by an increase in Fos expression within specific limbic regions (cingulate cortex, claustrum, piriform cortex, lateral septal nucleus, paraventricular nucleus of the thalamus, lateral habenula, and amygdala) as well as the basal ganglia (dorsomedial striatum and nucleus accumbens). In addition to this behavioral effect, conditioned subjects exhibited a significant increase in Fos expression within the cingulate cortex, claustrum, lateral septal nucleus, paraventricular nucleus of the thalamus, lateral habenula, and the amygdala, suggesting increased neuronal activity within these regions.  

The involvement of the excitatory neurotransmitter system in the lateral habenula and pedunculopontine nucleus in the initiation and propagation of limbic seizures induced by pilocarpine has been investigated in the rat. Limbic seizures occur in animals following bilateral microinjection into the lateral habenula of N-methyl-D-aspartate (NMDA) (5 and 12.5 nmol) or kainate (100 and 200 pmol), 15 min prior to a subconvulsant dose of pilocarpine (150 mg/kg, i.p.). In the absence of pilocarpine NMDA (5 and 12.5 nmol) or kainate (100 and 200 pmol), injected focally into the lateral habenula or pedunculopontine nucleus, produced sniffing, grooming and tremor but no electrographic or behavioural seizures. Behavioural and electrographic signs of limbic seizures following pilocarpine (380 mg/kg, i.p.) were attenuated or completely antagonized by focal injection into the lateral habenula of the NMDA antagonist, 2-amino-7-phosphonoheptanoate (AP7) (10 and 50 pmol) or kainate antagonist, gamma-D-glutamylaminomethylsulphonate (GAMS) (20 nmol).  

the septum, the area ventralis of Tsai, the lateral habenula, the optic tectum, the substantia grisea centralis, the nucleus tractus solitarii, the lateral medulla, the nucleus intercollicularis and in the archistriatum surrounding the nucleus robustus archistriatalis.  

The medial prefrontal cortex and lateral habenula contained more retrogradely labelled neurons from the LDT, whereas in the bed nucleus of the stria terminalis and central nucleus of the amygdala, more cells were labelled from the PPT.  

The major afferent to the medially adjacent MEA originates in the lateral habenula, while other putative afferents include the perifornical and lateral hypothalamic area, periaqueductal gray, superior colliculus, pontine reticular formation, and dorsal raphe nucleus. Afferents from the lateral habenula and contralateral superior colliculus represent extensions of more traditional basal ganglion circuitry which further delineate the MEA from the PPT.  

Dopamine (DA) and noradrenaline (NA) extracellular levels have been measured by microdialysis in the medial frontal cortex (MFC), nucleus accumbens (NAc) and caudate-putamen (CP) under baseline conditions in awake and halothane-anaesthetized rats, and after application of three types of stimuli which are likely to activate the brainstem catecholaminergic systems: mild stressors (handling and tail pinch), rewarded behavior (eating palatable food without prior food deprivation) and electrical stimulation of the lateral habenular nucleus. Stimulation of the lateral habenula induced a 2-3-fold increase in NA overflow in both MFC, NAc and CP but had no consistent effect on DA overflow in any region. The effect on NA release was abolished by a transection of the ipsilateral fasciculus retroflexus (which carries the efferent output of the lateral habenula).  

These areas were the lateral habenula, medial part; the sphenoid nucleus; and the stria medullaris.  

More widespread labeling was found in most hypothalamic subareas and in the lateral habenula.  

Slight to moderate binding was found together with slight to moderate mRNA levels in the majority of neurons in the anterior olfactory nucleus; septum, especially medial septum and diagonal band of Broca; amygdala, especially basolateral amygdala; lateral habenula; ventromedial hypothalamic nucleus; lateral interpeduncular nucleus; central gray, dorsal cochlear nucleus; parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal cord.  

Unilateral injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in the internal segment of the pallidum (GPi) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers ipsilaterally in the following thalamic nuclei: ventral anterior (VA), ventral lateral (VL), centromedian (CM), and lateral habenula (Hbl).  

Significantly fewer Fos-like IR cells were observed, however, in the lateral habenula of nighttime vs daytime non-stressed controls, resulting in a significantly greater percentage increase in Fos-like IR in the lateral habenula following nighttime vs daytime stress..  

Behavioral activation by either handling or electrical stimulation of the lateral habenula produced 2-3-fold increases in extracellular ACh-levels in the hippocampus similarly in all three groups.  

This suggests that in the dopamine-depleted rat, L-DOPA administration results in the stimulation of both D1 and D2 receptor systems, each capable of independently eliciting a full motor response, L-DOPA altered RCGU in the following brain regions ipsilateral to the lesion: entopeduncular nucleus (EP, + 105%), substantia nigra pars reticulata (SNr, + 121%), subthalamic nucleus (STN, + 32%), deep layers of the superior colliculus (DLSC, + 35%), and lateral habenula nucleus (LHN, -52%).  

In the cat, the effects of lateral habenula stimulation, at different ranges of frequency, on hippocampal units were studied. The results suggest an influence of lateral habenula to the hippocampus which does not appear to be cholinergically-mediated.  

basolateral amygdaloid nucleus, lateral habenula, hippocampus, dentate gyrus, entorhinal and cingulate cortices) and neocortical (e.g.  

Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose.  

The effects of internal pallidum and lateral habenula stimulation on epileptiform activity of cat's hippocampus were studied. The role of the lateral habenula and of the medial raphe as relay stations between the two regions is emphasized..  

Several areas had a higher concentration of cells that express connexin43, such as layer IA of the piriform cortex, supraoptic and paraventricular nuclei of the hypothalamus, anterior cortical amygdaloid nucleus, the reticular part of the substantia nigra, lateral habenula, mesencephalic trigeminal nucleus. Connexin32 mRNA was detected in discrete cell groups of the gray matter that appeared to be neurons, including cells in layer 2 of the neocortex, layer II of the piriform cortex, pyramidal cell layer of the hippocampus, granule and polymorphic cell layers of the dentate gyrus, islands of Calleja, olfactory tubercle, lateral thalamic nuclei, lateral habenula, and Purkinje cell layer of the cerebellar cortex.  

In contrast, the longer pulse duration gave rise to metabolic increases in several dopaminergic projections, including the frontal cortex, olfactory tubercle, and lateral habenula, and also enhanced activity in the lateral septal nucleus.  

In the thalamus, many positive cells were observed in the periventricular, reticular, lateral habenula, and reunions nuclei.  

Thus in limbic and related areas (CA2 and CA3 fields of the hippocampus, lateral habenula and septal nucleus) glucose utilization was reduced by 15-21%.  

Moderate concentrations of converting enzyme also occur in the paraventricular, medial habenula, lateral habenula and central median nuclei of the thalamus, the amygdala, the central gray, the locus coeruleus, the parabrachial nucleus and dorsal tegmental nucleus.  

Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula.  

Single shock stimulation of the lateral habenula (LHb) inhibited 89% of the tested DAergic neurons, most of which (83.8%) were also inhibited by PNS.  

Electrical stimulation of the lateral habenula (which has previously been identified as a powerful activator of the intrinsic hippocampal cholinergic and noradrenergic afferents) produced a similar increase in the release of these transmitters in the intact and grafted hippocampi.  

Inputs to LDTg were found from frontal cortex, diagonal band, preoptic areas, lateral hypothalamus, lateral mamillary nucleus, lateral habenula; the interpeduncular nucleus, ventral tegmental area, substantia nigra and retrorubral fields; the medial terminal nucleus, interstitial nucleus, supraoculomotor central grey, medial pretectum, nucleus of the posterior commissure, paramedian pontine reticular formation, paraabducens and paratrochlear region; the parabrachial nuclei and nucleus of the tractus solitarius. Terminal labelling from PHA-L injections of LDTg was found in infralimbic, cingulate and hippocampal cortex, lateral septum, septofimbrial and triangular nuclei, horizontal limb of diagonal band and preoptic areas; in the anterior, mediodorsal, reuniens, centrolateral, parafascicular, paraventricular and laterodorsal thalamic nuclei, rostral reticular thalamic nucleus, and zona incerta; the lateral habenula and the lateral hypothalamus.  

Significant levels of hybridization were also seen in the substantia nigra pars compacta, ventral tegmental area, lateral habenula, ventromedial hypothalamic nucleus and mammillary bodies.  

The lateral habenula receives massive afferents from dopamine-rich forebrain areas through the stria medullaris and sends efferents to mesencephalic dopaminergic systems through the fasciculus retroflexus. These results, along with other findings, indicate possibly that the pathways running through the entopeduncular nucleus, the stria medullaris, the habenula, probably the lateral habenula, and the fasciculus retroflexus are involved in a feedback loop from the striatum to the substantia nigra and regulate the activity of dopamine neurons..  

However, degenerating terminals were also present in areas not known to receive primary sensory innervation: the inferior olivary nucleus, sphenoid nucleus, medial and olivary pretectal nuclei, interpeduncular nucleus, interfascicular nucleus, caudal linear, dorsal, median, and paramedian raphe nuclei, supramammillary area, lateral habenula, ventrolateral geniculate nucleus, ventral reuniens nucleus, ventromedial hypothalamic nucleus, lateral hypothalamic and preoptic areas, suprachiasmatic nucleus, septohypothalamic nucleus, bed nucleus of the stria terminalis, lateral septal nucleus, accumbens shell, olfactory bulb, and retina.  

The graft-derived acetylcholine release was dependent on intact axonal impulse flow, and it was markedly increased during behavioral activation by sensory stimulation or by electrical stimulation of the lateral habenula.  

High levels of hybridization were also seen in the anterior olfactory nucleus, pyriform cortex, amygdala, some thalamic nuclei, especially the lateral habenula, the CA3 area of the hippocampal formation, the cingulate cortex, some components of the basal ganglia and associated areas, particularly the nucleus subthalamicus and the substantia nigra.  

Other telencephalic and diencephalic areas containing prominent, retrogradely labelled cells were the lateral septum, amygdala, zona incerta and lateral habenula.  

The results demonstrate that dystonia is associated with marked increases in 2-DG uptake in the constituent nuclei of the basal ganglia (caudate nucleus, putamen, medial and lateral segments of the globus pallidus) and in the subthalamic nucleus, but decreased uptake in the structures that receive output of the basal ganglia (ventral anterior/ventral lateral thalamic complex and lateral habenula).  

Projections from 26 of these regions are supported by available orthograde tracing data; the cingulate cortex, bed nucleus of stria terminalis, medial septum and diagonal band of Broca, ventral pallidum, medial and lateral preoptic areas, lateral hypothalamus, dorsomedial nucleus of hypothalamus, lateral habenula, interpeduncular nucleus, substantia nigra, central (periaqueductal) gray, and laterodorsal tegmental nucleus seem to represent major sources of afferents to the median-paramedian raphe complex. The most prominent labelling was observed in the lateral habenula and the interpeduncular nucleus, but retrogradely labelled cells were also noted in the medial and lateral preoptic areas, lateral and dorsal hypothalamus, ventral tegmental area, laterodorsal tegmental nucleus, medial parabrachial nucleus, and the pontine tegmentum. Excitatory amino acid inputs from lateral habenula and interpeduncular nucleus may play predominant roles in the control of ascending serotonergic and non-serotonergic projections originating in the median and paramedian raphe nuclei..  

Behavioural activation by electrical stimulation of the lateral habenula resulted in a 4-fold increase in acetylcholine release in normal animals, and this response was totally blocked by a transection of the lateral habenular efferents running in the fasciculus retroflexus. The levels obtained by lateral habenula stimulation were reduced by about 95% in the rats with fimbria-fornix lesions. No changes could be detected after atropine, handling, lateral habenula stimulation, or acute fimbria-fornix or fasciculus retroflexus transection.(ABSTRACT TRUNCATED AT 400 WORDS).  

Intracerebral microdialysis has revealed that acetylcholine and noradrenaline release is restored to normal or supranormal levels in the graft-reinnervated hippocampus, and that the grafted neurons can be activated in a normal way from the host through behavioural activation induced by sensory stimulation or electrical stimulation of the lateral habenula.  

Conversion of GU values to standard scores showed abnormalities in dt compared with both control groups in the following areas: deep cerebellar nuclei, locus coeruleus, pontine gray, ventrolateral-ventromedial thalamic complex, nucleus of the third nerve, lateral habenula, and basolateral amygdala.  

The limbic system showed decrements in the medial cortex and hippocampal dentate gyrus (outer blade) and the lateral habenula, while there was stimulation in the mammillary body and the basolateral amygdaloid nucleus.  

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