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At least 19 recordsLinked to original sources
PubMed1983

Cholinergic and GABAergic forebrain projections to the habenula and nucleus interpeduncularis: surgical and kainic acid lesions.

The forebrain cholinergic and GABAergic projections to the habenula and nucleus interpeduncularis have been investigated by means of surgical and kainic acid lesions. Bilateral transection of the stria medullaris caused a 50% decrease of choline acetyltransferase in both the habenula and nucleus interpeduncularis, and a 65% decrease of glutamate decarboxylase in the habenula. Electrolytic lesions of the posterior septum (nucleus triangularis septi and nucleus septo-fimbrialis) accounted for at least 30-40% decrease of the cholinergic parameter in the habenula and nucleus interpeduncularis. Moreover, the choline acetyltransferase decrease in the habenula appeared restricted to the medial part of the nucleus. Kainic acid injections causing very large neuronal destruction in the nucleus of the diagonal band of Broca, and more than 70% decrease of choline acetyltransferase in the dorsal hippocampus, did not affect the cholinergic parameter in either the medial or lateral habenula or nucleus interpeduncularis. Kainic acid injections in the nucleus entopeduncularis resulted in a 40% decrease of glutamate decarboxylase in the habenula. Kainic acid injections in the nucleus of the diagonal band were accompanied by a 40% decrease of glutamate decarboxylase in the medial subdivision only. The present study points at the nuclei of the posterior septum as the source of a major cholinergic projection to the habenula and nucleus interpeduncularis, and reveals a previously unsuspected GABAergic input from the nucleus of the diagonal band to the medial habenula.

Acetylcholine↗
PubMed1999

Nitric oxide synthase activity reveals an asymmetrical organization of the frog habenulae during development: A histochemical and cytoarchitectonic study from tadpoles to the mature Rana esculenta, with notes on the pineal complex.

In the adult frog, structural asymmetry of the left dorsal habenula in respect to the right counterpart has been repeatedly documented in previous studies. In the present investigation, histochemical expression of beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was examined in the habenulae of the developing and adult Rana esculenta. In tadpoles and during metamorphosis, selective neuropil staining was consistently found within a lateral compartment of the medial subnucleus of the left dorsal habenula. The staining was still present in the same location, but much less intense, in the mature frog, indicating that the neurochemical pattern observed during development was at least in part transient. Thus, the present data point out a peculiar neurochemical pattern of the habenular asymmetry in the frog, suggesting that nitric oxide may be involved in the developmental shaping which leads to an asymmetrical configuration of the habenulae. In addition, NADPH-diaphorase-positive cells were detected in the frontal organ (the extracranial component of the pineal complex in strict relationship with the habenulae in the frog), and labeled fibers were found in the frontal nerve, which arises from the frontal organ. This latter finding supports the postulated relationship of the habenular asymmetry with the occurrence of the frontal organ. The finding of NADPH-diaphorase histochemical reactivity confined to a distinct portion of the medial subnucleus of the left dorsal habenula prompted a reexamination of the cytoarchitecture of the developing and mature habenular complex in the frog. The bicompartmentalization detected with histochemistry in the medial subnucleus of the left dorsal habenula of the developing and adult frog was fully supported by the study of Nissl-stained epithalamic sections. These data point out that the left-right structural differences of the frog habenular complex are more complex than previously believed, and may be subserved by chemically regulated developmental processes.

Animals↗
PubMed1998

The triangular septal nucleus as the major source of ATP release in the rat habenula: a combined neurochemical and morphological study.

The role of ATP as a fast neurotransmitter is emerging from several lines of physiological and pharmacological studies. The bulk of experimental data on release properties and purinergic receptor-mediated postsynaptic potentials derives from studies in the habenula, but the source of the stimulation-evoked ATP release in this region is still unknown. In the present study, retrograde and anterograde tracing techniques were used to establish that both calretinin-containing and calretinin-negative neurons in the triangular septal and septofimbrial nuclei send a massive projection to the medial habenula, where they form asymmetrical synapses with their target neurons. The cells of origin, their axon terminals, as well as their synaptic targets remained unstained in sections immunostained for GABA. Electrolytic lesions of this anatomically circumscribed pathway resulted in an over 80% decrease in ATP release from habenula slices evoked by electric field stimulation. The possibility of transneuronal effects and release from local collaterals of habenular projection neurons accounting for the decreased ATP release has been excluded, since (i) there were no signs of neuronal degeneration, chromatolysis or atrophy in the habenula, (ii) the projection neurons have extremely sparse local collaterals and (iii) there are apparently no interneurons in the habenula. We conclude that the projection from the triangular septal and septofimbrial nucleus to the habenula uses ATP as a fast neurotransmitter, and its co-transmitter, if any, is likely to be glutamate.

Adenosine Triphosphate↗
PubMed1994

Habenula lesions decrease the responsiveness of dorsal raphe serotonin neurons to cocaine.

The median and dorsal (MR and DR) raphe nuclei are the origin of serotonin (5-HT)-containing neurons that innervate the forebrain. Neurons originating in the medial and lateral habenula provide an extensive afferent input to the midbrain that could serve as a negative feedback circuit. The present study was undertaken to establish whether intact habenula nuclei are required to observe the depressant effects of cocaine on the neural activity of 5-HT somata in the DR. To this end, the spontaneous activity of DR 5-HT neurons was assessed in male rats that had previously received bilateral radiofrequency lesions of the habenula complex either 1-4 h (short term) or 7 days (long term) prior to extracellular recordings of single 5-HT neurons of the DR. In rats with short-term lesions, the inhibitory response to cocaine was significantly attenuated. The mean dose to inhibit activity by 50% (ID50) was increased from 0.68 mg/kg in controls to 2.5 mg/kg in lesioned rats. Short-term habenula lesions also significantly decreased the numbers (but not the firing rates) of 5-HT neurons encountered in the DR. In contrast, the dose-response to cocaine as well as the numbers and firing rates of 5-HT neurons found in rats with long-term habenula lesions did not differ from controls. These results suggest that the inhibitory effects of cocaine on DR 5-HT neuronal activity depend in part on the ability of cocaine to affect habenula control of raphe 5-HT function.

Animals↗
PubMed1999

Prenatal cocaine produces signs of neurodegeneration in the lateral habenula.

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. On day 17 of gestation, dams were implanted with two silicone pellets, each containing either vehicle or one of 2 doses of cocaine (80 mg or 55 mg per pellet). 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. When similarly treated vehicle- and cocaine-exposed animals were tested behaviorally at 60 days of age, they did not differ on measures of open field activity, open arm avoidance on the elevated plus-maze or conditioned place preference for cocaine, although a linear trend analysis indicated some hyperactivity of the cocaine-pretreated pups during the place preference test. These results indicate that continuous cocaine exposure has selective neurotoxic effects on the habenula of the developing fetus similar to cocaine's effects in the adult.

Animals↗
PubMed1990

Habenula as a relay in the descending pathway from nucleus accumbens to periaqueductal grey subserving antinociception.

This study explored the possibility of a relay at habenula for the descending neural pathway of antinociception. The latency of the escape response elicited by radiant heat on the snout of the rabbit was taken as index of nociception. (1) Microinjection of 20 micrograms of morphine into nucleus accumbens resulted in a one-fold increase in nociceptive threshold 20-40 min after the injection. This effect of morphine was markedly attenuated by naloxone or met-enkephalin antiserum administered to the nucleus habenula, suggesting that the release of met-enkephalin in habenula is essential for the antinociception induced by morphine injected into nucleus accumbens. (2) Injection of 10 micrograms of morphine into habenula produced a significant increase in escape response latency 20-40 min after the injection. This antinociceptive effect of morphine was attenuated by naloxone or muscimol, and enhanced by bicuculline methochloride administered to periaqueductal grey, suggesting that morphine may act on habenula to activate a descending neural pathway extending to periaqueductal grey to induce an antinociceptive effect, which seems to utilize endogenous opioid peptides and gamma-aminobutyric acid as its mediators. Taking together, the results suggest that habenula is an important relay in the descending neural pathway from nucleus accumbens to periaqueductal grey subserving antinociception.

Animals↗
PubMed1999

Covariation of activity in habenula and dorsal raphé nuclei following tryptophan depletion.

Abnormal serotonergic function is implicated in the pathogenesis of affective disorders. We induced transient depressive relapses in volunteer patients by rapidly depleting plasma tryptophan, the precursor of serotonin (5-HT), and measured neural activity during different cognitive tasks using positron emission tomography (PET). Neural activity in several 5-HT-related brain areas, e.g., dorsal raphé, habenula, septal region, amygdala, and orbitofrontal cortex, covaried significantly with plasma levels of tryptophan and ratings of depressed mood. Task-specific responses in left amygdala and left anterior cingulate were attenuated by tryptophan depletion. We used these PET data to test the hypothesis that projections from the habenula modulate dorsal raphé activity and that this modulation is enhanced in patients experiencing a profound mood change following serotonergic challenge. A strong linear correlation (r(2) > 0.5) between habenula and raphé activity was observed in subjects with postdepletion ratings >/=10 on a modified Hamilton depression scale, whereas subjects experiencing milder changes in mood had weaker habenula-raphé coupling (r(2) < 0.5). These data support a model of the serotonergic system in which the habenula projection to the raphé represents a convergent feedback pathway that controls the release of 5-HT throughout the brain. In our experiment we were able to engage this system in patients who were sensitive to tryptophan depletion.

Adult↗
PubMed1994

Afferent and efferent connections of the habenula in the larval sea lamprey (Petromyzon marinus L.): an experimental study.

The habenula is an integrative center between the striatum and the limbic and motor systems. With the aim of achieving further understanding of the evolution of this structure in vertebrates, we carried out an experimental study of the afferent and efferent connections of the habenula of larval sea lamprey. Experimental procedures included in vivo and in vitro transport after injections of horseradish peroxidase (HRP) into the habenula, telencephalon, pineal organ, dorsal thalamus, and posterior tubercle as well as carbocyanine dye tracing (DiI). The combined results of these experiments showed that the pattern of habenular connections is very simple. Most afferents appear to originate from the lobus subhippocampalis and neighboring area, whereas the only efferents found coursed in the fasciculus retroflexus to the neuropil of the nucleus interpeduncularis. This neuropil comprises a commissural region in the rostral mesencephalon, two long bilateral areas extending in the basal mesencephalon and medulla oblongata to the trigeminal level, and, finally, a caudal commissural zone. The conspicuous habenular commissure contains interhemispheric fibers that appear to form occasional contacts within the habenulae. The lamprey habenula also receives a few immunocytochemically identified fibers (somatostatinergic, catecholaminergic, and serotoninergic fibers) from other sources.

Afferent Pathways↗
PubMed1994

Developmental regulation of multiple nicotinic AChR channel subtypes in embryonic chick habenula neurons: contributions of both the alpha 2 and alpha 4 subunit genes.

Habenula neurons from both early and late stage embryonic chickens express multiple subtypes of nicotinic acetylcholine receptor channels (nAChRs). The channel subtypes expressed by habenula neurons are similar in functional properties, but apparently distinct in subunit composition, from their peripheral counterparts in autonomic ganglia. Early in development, nicotine activates four classes of neuronal bungarotoxin (nBGT)-sensitive channels (approx. conductance = 15, 30, 50, 60pS) that are intermingled on the surface of habenula neuronal somata. In neurons removed from older animals, nAChR channel activity has increased 4- to 40-fold and channel subtypes have become spatially segregated from one another. Analysis of the profile of nAChR subunit gene expression by polymerase chain reaction indicates that several of the alpha-type subunit genes, including alpha 2,3,4,5,7, and alpha 8, as well as both beta 2 and beta 4, are expressed. Treatment of the neurons with subunit specific antisense oligonucleotides reveals that the alpha 2 and alpha 4 (but not alpha 3) subunits contribute to the functional profile of native nAChRs expressed by habenula neurons. Consideration of the functional properties and apparent subunit composition of autonomic ganglion nAChRs in the chick suggests that habenula neurons may utilize a very distinct set of subunit combinations to produce an array of nAChR channel subtypes similar in both conductance and pharmacological profile to those expressed by sympathetic neurons.

Acetylcholine↗
PubMed1984

Evidence for a dopaminergic innervation of the cat lateral habenula: its role in controlling serotonin transmission in the basal ganglia.

The presence of a dopaminergic innervation of the cat lateral habenula and its possible role in modulating serotonin transmission within the basal ganglia were investigated using both in vitro and in vivo approaches. A high density of [3H]spiroperidol binding sites with similar affinities for domperidone and apomorphine as those present in the cat striatum were found in the habenula. By means of the push-pull cannula technique, a substantial release of [3H]dopamine continuously formed from [3H]tyrosine was detected in the lateral habenula of halothane-anesthetized cats since the amount of [3H]catecholamines was enhanced in the presence of benztropine, an inhibitor of dopamine uptake into dopaminergic nerve terminals. Furthermore, in anesthetized animals with a push-pull cannula implanted in each caudate nucleus and substantia nigra habenular applications of dopamine (10(-7) M) reduced nigral but not striatal release of [3H]serotonin continuously formed from [3H]tryptophan. This change was prevented either by the delivery of domperidone to the lateral habenula or by the blockade of GABAergic transmission (picrotoxin 10(-5) M) in the dorsal raphe. These data support the involvement of habenulo-raphe pathways in the regulation of serotonin transmission in the cat basal ganglia and indicate that dopaminergic inputs to the lateral habenula participate in such a control.

Animals↗
PubMed1994

Stimulant-induced psychosis, the dopamine theory of schizophrenia, and the habenula.

While one of the original underpinnings of the dopamine theory of schizophrenia was the paranoid psychosis which often develops during the binges or speed runs of chronic amphetamine addicts (and, more recently, in cocaine addicts), neurochemical studies of such drug abusers or from animals given continuous stimulants in an effort to model stimulant psychoses have not played a major role in the further evolution of this theory. One clear persisting alteration produced by continuous amphetamine is a neurotoxicity to dopaminergic innervations in caudate. Yet continuous cocaine administration apparently does not induce a similar neurotoxicity and this makes this effect a poor candidate for an underpinning of stimulant psychoses. 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. This finding has led to a reconsideration of the role of these structures in psychoses. The habenula, as the chief relay nucleus of the descending dorsal diencephalic system (consisting of stria medullaris, habenula and fasciculus retroflexus), is an important link between limbic and striatal forebrain and lower diencephalic and mesencephalic centers. Studies of glucose utilization have consistently shown the habenula to be highly sensitive to dopamine agonists and antagonists. Lesions of habenula produce a wide variety of behavioral alterations. The dorsal diencephalic system has major and predominantly inhibitory connections onto dopamine-containing cells and it mediates part of the negative feedback from dopamine receptors onto dopamine cell bodies. It represents one of the major inputs in brain to the raphe nuclei and has anatomical and functional connections to modulate important functions such as sensory gating through thalamus, pain gating through central gray and raphe and motor stereotypies and reward mechanisms through substantia nigra and the ventral tegmental area. It is argued that alterations in these pathways are ideal candidates for producing the behaviors which occur during psychosis and that future considerations of the circuitry underlying psychoses need to include this highly important but relatively neglected system.

Animals↗
PubMed1996

Simultaneous recording of spontaneous activities and nociceptive responses from neurons in the pars compacta of substantia nigra and in the lateral habenula.

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.

Action Potentials↗
PubMed1975

Indolamine metabolism in the intact and denervated pineal, pineal stalk and habenula.

Indolamine metabolism in the rat pineal is regulated by central influences mediated through the superior cervical sympathetics. The pineal stalk and medial habenular nucleus also have serotonin-containing cells and an innervation from the superior cervical ganglion (SCG). The present study was carried out to determine if the habenula and pineal stalk are similar to the pineal in certain aspects of indolamine metabolism. No diurnal rhythm in habenular serotonin content was observed, but ganglionectomy or decentralization of SCG results in a significant increase in habenular serotonin content. Unlike the pineal, the habenula and pineal stalk exhibit no rhythm in N-acetyltransferase (N-AT) activity; the activity of the enzyme in those tissues is comparable to low values of the diurnal rhythm in the pineal. N-AT activity in the pineal stalk and habenula is unaffected by sympathectomy. Similarly, there is little, if any, hydroxyindole-O-methyltransferase (HIOMT) activity in the pineal stalk and habenula; unlike the pineal, it is unaffected by continuous environmental lighting conditions or sympathectomy. These observations indicate that neither the pineal stalk nor the habenula represents a 'deep' pineal in the rat but that habenular indolamine metabolism is regulated by its peripheral sympathetic innervation.

Acetylserotonin O-Methyltransferase↗
PubMed1982

Involvement of lateral habenula-dorsal raphe neurons in the differential regulation of striatal and nigral serotonergic transmission cats.

The importance of the lateral habenula-dorsal raphe pathway in the control of in vivo [3H]serotonin release in the cat basal ganglia was examined using the push-pull cannula technique and an isotopic method for the estimation of [3H]serotonin continuously formed from [3H]tryptophan. [3H]Serotonin was measured in both caudate nuclei and substantiae nigra and, in some cases, in the dorsal raphe. Electrical stimulation of the lateral habenula decreased [3H]serotonin release in all structures studied. Blockade of the GABA inhibitory pathway to the lateral habenula by the local application of picrotoxin reduced [3H]serotonin release in both substantiae nigra and increased release of the 3H-amine in the dorsal raphe but was without effect on [3H]serotonin release in either caudate nucleus. This inhibition of nigral [3H]serotonin release was antagonized by simultaneous application of picrotoxin to the dorsal raphe. Substance P delivery to the dorsal raphe produced the same effects on [3H]serotonin release as described for picrotoxin application to the lateral habenula except that inhibition of nigral [3H]serotonin release was not prevented by local co-administration of picrotoxin. These results suggest that the lateral habenula can control serotonergic transmission in the basal ganglia and that this regulation may be different for those serotonergic neurons innervating the caudate nucleus versus those projecting to the substantia nigra.

Animals↗
PubMed1996

Afferent and efferent connections of the habenula in the rainbow trout (Oncorhynchus mykiss): an indocarbocyanine dye (DiI) study.

The habenula is a conserved structure in the brain of vertebrates. With the aim of further understanding of the evolution of the habenular system in vertebrates, we studied the afferent and efferent connections of the habenula of the rainbow trout. Experiments included application of the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) into the habenula, telencephalon, pineal organ, posterior tubercle, and interpeduncular nucleus (IPN). The results obtained reveal a consistent pattern of habenular connections. Most afferents originate from three nuclei, one extending from the preoptic region to the rostral thalamus (the entopeduncular nucleus), the second located in the region of the hypothalamus-posterior tubercle and consisting of large bipolar cells (tuberculohabenular nucleus), and the third in the preoptic region (preoptic nucleus). A few large neurons of the locus coeruleus appeared to be labeled in some cases. The trout habenula also receives pineal and parapineal projections. Small labeled glial cells were observed in the thalamus around the fasciculus retroflexus and, sometimes, around the IPN. The most conspicuous efferents coursed in the fasciculus retroflexus to the IPN, the isthmal raphe, and the central gray. The existence of olfactohabenular or habenulotelencephalic projections is discussed.

Afferent Pathways↗
PubMed2001

Nicotine produces selective degeneration in the medial habenula and fasciculus retroflexus.

Nicotine's neurotoxic properties in rats were investigated by administering (-)-nicotine tartrate for 5 days either continuously in doses of 5.01, 5.72, 6.44, 7.13, 20.41 and 43.1 mg/kg/day via osmotic minipump or intermittently at 11.32 mg/kg/day via one daily subcutaneous injection. As assessed by silver staining, neurotoxicity was seen almost exclusively in the axons of the medial habenula and its output tract, the fasciculus retroflexus, in all treatment groups except the lowest dose. Within the habenula, the damage was noted in the ventral-medial-most portion of the nucleus which is thought to be dense with the alpha 4 beta 2 and/or alpha 3 beta 4 receptor subtypes. Past research has shown the medial habenula to be highly sensitive to the effects of nicotine, and these findings, in conjunction with related research using dopaminergic stimulants, indicate that the habenula may be a weak link in the neurotoxicity seen following stimulant drugs of abuse.

Animals↗
PubMed1981

Growth of fresh volumes and spontaneous cell death in the nuclei habenulae of albino rats during ontogenesis.

The growth of the nuclei habenulae medialis et lateralis of albino rats is described by monotonically increasing growth curves of fresh volumes during ontogenesis. The nucleus habenulae medialis matures earlier than the nucleus habenulae lateralis in the perinatal period. However, the two nuclei reach their final volume at about the same time. Simultaneous electron microscopic investigation reveals the phenomenon of spontaneous nerve cell degeneration within the nuclei habenulae during ontogenesis in spite of the non-overshooting growth curves for the habenular nuclei.

Animals↗
PubMed1992

Excitatory neurotransmitters in the lateral habenula and pedunculopontine nucleus of rat modulate limbic seizures induced by pilocarpine.

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. Limbic seizures also occur after a subconvulsant dose of pilocarpine when it is preceded by injection of NMDA (5 and 12.5 nmol) or kainate (50, 100 and 200 pmol) into the pedunculopontine nucleus. 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). In addition, AP7 (0.05, 0.1 and 1.0 nmol) or GAMS (40 nmol) injected into the pedunculopontine nucleus suppressed limbic seizures induced by i.p. administration of pilocarpine (380 mg/kg). The relative efficacy of NMDA and non-NMDA receptor antagonists revealed that the selective NMDA antagonist, AP7, was more potent in its anticonvulsant activity in comparison to GAMS, a non-NMDA receptor antagonist.

2-Amino-5-phosphonovalerate↗