LHb Neurons Research Articles

AKAP150-anchored PKA regulates synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the mouse lateral habenula

The scaffolding A-kinase anchoring protein 150 (AKAP150) is critically involved in kinase and phosphatase regulation of synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a key role in brain’s processing of rewarding/aversive experiences, however its role in the lateral habenula (LHb, as an important brain reward circuitry) is completely unknown. Using whole cell patch clamp recordings in LHb of male wildtype and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), here we show that the genetic disruption of PKA anchoring to AKAP150 significantly reduces AMPA receptor-mediated glutamatergic transmission and prevents the induction of presynaptic endocannabinoid-mediated long-term depression in LHb neurons. Moreover, ΔPKA mutation potentiates GABAA receptor-mediated inhibitory transmission while increasing LHb intrinsic excitability through suppression of medium afterhyperpolarizations. ΔPKA mutation-induced suppression of medium afterhyperpolarizations also blunts the synaptic and neuroexcitatory actions of the stress neuromodulator, corticotropin releasing factor (CRF), in mouse LHb. Altogether, our data suggest that AKAP150 complex signaling plays a critical role in regulation of AMPA and GABAA receptor synaptic strength, glutamatergic plasticity and CRF neuromodulation possibly through AMPA receptor and potassium channel trafficking and endocannabinoid signaling within the LHb.

Transcranial direct current stimulation of the prefrontal cortex improves depression-like behaviors in rats with Parkinson's disease

Depression associated with Parkinson's disease (PD) seriously affects patients, and there is a lack of effective treatments. Transcranial direct current stimulation (tDCS) is increasingly used as a new non-invasive neuromodulation technique in the treatment of neuropsychiatric diseases. However, there is a paucity of research on tDCS for PD-related depression. Our study used PD model rats established with unilateral destruction of the medial forebrain bundle (MFB) to observe the modulatory effects of tDCS acting on the mPFC on depression-like behaviors. We found that tDCS acting on the mPFC improved depression-like behaviors in PD model rats by increasing sucrose intake in sucrose preference test (n = 7–10 rats/group) and shortening immobility time in forced swimming test (n = 7–8 rats/group). Meanwhile, tDCS decreased the expression of c-Fos protein (n = 8–11 rats/group) and the excitation of glutamatergic neurons (n = 6–8 rats/group) in the PrL and LHb of PD model rats. Western blots showed that tDCS decreased the overexpression of serine 845 phosphorylation site of AMPA receptor GluR1 (p-GluR1-S845) in the PrL and LHb of PD model rats (n = 8–11 rats/group), and the overexpression of p-GluR1-S831 in the LHb (n = 8–11 rats/group). The results of this study show that tDCS acting on the mPFC helps to improve PD-related depression, which involves the modulation of excitability and AMPA receptor phosphorylation on the PrL and LHb neurons.

A neural substrate for negative affect dictates female parental behavior

Parental behaviors secure the well-being of newborns and concomitantly limit negative affective states in adults, which emerge when coping with neonatal distress becomes challenging. Whether negative-affect-related neuronal circuits orchestrate parental actions is unknown. Here, we identify parental signatures in lateral habenula neurons receiving bed nucleus of stria terminalis innervation (BNSTLHb). We find that LHb neurons of virgin female mice increase their activity following pup distress vocalization and are necessary for pup-call-driven aversive behaviors. LHb activity rises during pup retrieval, a behavior worsened by LHb inactivation. Intersectional cell identification and transcriptional profiling associate BNSTLHb cells to parenting and outline a gene expression in female virgins similar to that in mothers but different from that in non-parental virgin male mice. Finally, tracking and manipulating BNSTLHb cell activity demonstrates their specificity for encoding negative affect and pup retrieval. Thus, a negative affect neural circuit processes newborn distress signals and may limit them by guiding female parenting.

High frequency stimulation of the subthalamic nucleus: linking mood and motor effects at the level of the basal ganglia and 5-HT system

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a neurosurgical procedure commonly used for the management of severe movement disability in advanced Parkinson’s disease (PD), but some patients experience debilitating psychiatric effects that have an uknown neural origin. Here we use animal models to uncover effects of DBS of the STN on the lateral habenula nucleus (LHb), a fast emerging controller of motivational and emotive behaviours, and a major source of input to 5-HT neurons in the dorsal raphe nucleus (DRN). STN stimulation at clinical parameters, consistently modulated the firing of the majority of LHb neurons tested. LHb neurons projecting to the DRN were identified using antidromic activation, and were also modulated by STN stimulation. Juxtacellular labelling confirmed that STN-responsive neurons were LHb glutamatergic neurons. We identified a behavioural correlate of the neurophysiological effects of STN stimulation. Thus, STN stimulation induced a behaviourally selective decrease in food and sucrose intake, consistent with a reduced motivational state. Moreover, the use of neurotoxic lesions demonstrated that these STN-evoked responses were dependent on both the LHb and 5 HT. Collectively, the present data demonstrate that DBS of the STN influences the LHb and its pathway to the midbrain 5-HT system to generate decreases in motivational outputs. Thus, the impact of the STN on a major controller of motivational and emotive behaviours offers an unexpected route by which STN stimulation might evoke psychiatric effects in patients with PD.

Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice

The dorsal raphe nucleus (DRN) is a key site for 5-hydroxytryptamine (5-HT) synthesis and release. DRN dysfunction has been implicated in several stress-related disorders, including depression and anxiety. The lateral habenular nucleus (LHb) has been shown to inhibit the activity of DRN 5-HT neurons, and thus the LHb-DRN pathway plays an important role in the pathogenesis of depression. Although it is known that the LHb also receives the projection from the 5-HT neuron in the DRN, whether 5-HT neurons in the DRN can influence activity of the LHb in vivo and whether this effect is related to the induced behavioral changes have not been investigated. In the current study, we determined how injecting γ-aminobutyric acid (GABA) into the DRN to inhibit 5-HT neurons affected behavior and the changes in the activity of LHb neurons in mice. We found that GABA injection into the DRN induced depression-like behavior in mice, as indicated by increased immobility time, and decreased climbing time in the forced swimming test and the tail suspension test, decreased time spent in the center and total distance moved in the open field test. Using extracellular single unit recording, we showed that the firing rate of LHb neurons decreased after GABA microinjection into the DRN. Further, c-Fos expression in LHb neurons was inhibited. Together our results indicate that inhibition of DRN 5-HT neurons can cause decreased LHb activity and depression-like behavior in mice, however this depression-like behavior could be independent of the LHb activity. The observed decrease in LHb activity is probably due to the presence of a negative feedback loop between the DRN and the LHb, which may play a role in maintaining emotional homeostasis.

High-frequency stimulation of the subthalamic nucleus modulates neuronal activity in the lateral habenula nucleus.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is often used to treat movement disability in advanced Parkinson's disease, but some patients experience debilitating psychiatric effects including depression. Interestingly, HFS of the STN modulates 5-HT neurons in the dorsal raphe nucleus (DRN) which are linked to depression, but the neural substrate of this effect is unknown. Here, we tested the effect of STN stimulation on neuronal activity in the lateral habenula nucleus (LHb), an important source of input to DRN 5-HT neurons and also a key controller of emotive behaviours. LHb neurons were monitored in anaesthetized rats using single-unit extracellular recording, and localization within the LHb was confirmed by juxtacellular labelling. HFS of the STN (130Hz) evoked rapid changes in the firing rate of the majority of LHb neurons tested (38 of 68). Some LHb neurons (19/68) were activated by HFS, while others (19/68), distinguished by a higher basal firing rate, were inhibited. LHb neurons that project to the DRN were identified using antidromic activation and collision testing (n=17 neurons). Some of these neurons (5/17) were also excited by HFS of the STN, and others (7/17) were inhibited although this was only a statistical trend. In summary, HFS of the STN modulated the firing of LHb neurons, including those projecting to the DRN. The data identify that the STN impacts on the LHb-DRN pathway. Moreover, this pathway may be part of the circuitry mediating the psychiatric effects of STN stimulation experienced by patients with Parkinson's disease.

Transcriptomic-anatomic analysis of the mouse habenula uncovers a high molecular heterogeneity among neurons in the lateral complex, while gene expression in the medial complex largely obeys subnuclear boundaries

The mammalian habenula with its medial and lateral complexes has gained much interest in recent years, while knowledge on the detailed biological functions of these nuclei is still scarce. Novel strategies to differentiate and identify habenular cell types are required. Such attempts have largely failed, most likely due to the lack of appropriate molecular markers. One important tool to approach this dilemma is available in form of the Allen Brain Atlas (ABA), which provides detailed expression patterns of many genes in the mouse brain. In the present report, ABA tools in combination with visual inspection of ISH images were used to detect transcripts, which are strongly expressed in medial (MHb) and lateral (LHb) habenular complexes. Against our expectations, most transcripts were differentially distributed throughout the LHb, disregarding boundaries of subnuclear areas. Nine distinct distribution patterns were recognized. Yet, several transcripts could not be attributed to one of these, suggesting a high diversity of neuron types in the LHb. In the MHb, in contrast, many transcripts tended to obey subnuclear boundaries. The differential distribution of others like Adcyap1, Chrna3, or Trp53i11 suggests the presence of a novel subfield adjacent to the region of the MHbVm, which now is termed intermediate field of the ventral MHb. In addition, the localizations of Amigo2, Adcyap1, and a couple of other transcripts suggest a lateral extension of the MHb, which is here, termed HbX area. Apparently, this area is composed of intermingled MHb and LHb neurons and may allow functional interaction between the both habenular complexes.

The lateral habenular nucleus mediates signal transduction from the insular cortex in OSA rats

The insular cortex (Ic) and habenular nuclei (Hb) of the limbic system are associated with human and animal dyspnea by regulating 5-hydroxytryptamine (5-HT) release in the raphe nuclei (RN). However, the Hb are composed of the medial habenular nucleus (MHb) and the lateral habenular nucleus (LHb). Therefore, it is still unclear whether the Ic signal is conducted through the MHb or LHb. This study aimed to investigate the role of the Hb and Ic in obstructive sleep apnea syndrome (OSA) and the functional relationship between these two structures. We monitored multiple indicators, including the respiration movement curve, neuronal activity in the MHb and LHb, and arterial blood gas, when stimulating the anterior Ic of Wistar rats. We compared the results with the control group (stimulating the surrounding cortex). Electrical stimulation of the Ic in the rat brain caused respiratory disturbances, apnea, reduced blood pH, and aggravated base deficit (more negative base excess value) compared to control animals (p < 0.05). It also reduced the spontaneous firing of the MHb neurons but increased that of the LHb neurons. Electrical stimulation of the Ic induces apnea in rats in a similar manner to human OSA. The Ic and the Hb are functionally linked. Stimulation of the Ic inhibits the MHb, but activates the LHb. It induces OSA-like symptoms by enhancing LHb-mediated inhibition of the RN. This study illustrates the mechanism by which an animal model of OSA is created by stimulating the Ic and promotes understanding of OSA pathogenesis.

The lateral habenula is a common target of cocaine and dexamethasone

The lateral habenular nucleus (LHb) receives projections from areas rich in dopaminergic neurons and sends efferent fibers to these areas, suggesting that the LHb has a role in dopaminergic reward-related activity. The LHb is also implicated in multiple stress reactions, including responses to painful stimuli. However, it is unclear whether the LHb facilitates glucocorticoid/cocaine interactions by serving as a common target of both. In this study we investigated the effect of cocaine and dexamethasone (a synthesized glucocorticoid) on pain-related neurons (pain-excitatory and pain-inhibitory). Cocaine treatment effectively increased the firing rate of 89.7% of pain-excitatory neurons (cocaine-up response) and decreased the firing rate of 81.8% of pain-inhibitory neurons (cocaine-down response) in the LHb, suggesting that LHb neurons respond to cocaine via different mechanisms. Dexamethasone enhanced the firing rate of the cocaine-up neurons, while cocaine-down neurons were not influenced, indicating that both drugs may elicit an electrophysiological response at the same LHb neuron. Effects of either cocaine or dexamethasone alone, or both combined, on FOS expression in the LHb were observed via immunohistochemistry. Single administration of either cocaine or dexamethasone increased the number of FOS-positive neurons in the LHb. Pretreatment with dexamethasone and then cocaine markedly enhanced the number of FOS-positive neurons in the LHb relative to cocaine treatment alone, suggesting that stress and addictive drugs exert a synergistic effect on the LHb. We conclude that the LHb responds to cocaine via more than one mechanism and is a common target of both cocaine and the dexamethasone.

Individual neurons in the rat lateral habenular complex project mostly to the dopaminergic ventral tegmental area or to the serotonergic raphe nuclei

The lateral habenular complex (LHb) is a bilateral epithalamic brain structure involved in the modulation of ascending monoamine systems in response to afferents from limbic regions and basal ganglia. The LHb is implicated in various biological functions, such as reward, sleep-wake cycle, feeding, pain processing, and memory formation. The modulatory role of the LHb is partially assumed by putative spontaneously active LHb neurons projecting to the dopaminergic ventral tegmental area (VTA) and to the serotonergic median (MnR) and dorsal raphe nuclei (DR). All four nuclei form a complex and coordinated network to evoke appropriate responses to reward-related stimuli. At present it is not known whether individual LHb neurons project to only one or to more than one monoaminergic nucleus. To answer this question, we made dual injections of two different retrograde tracers into the rat VTA and either DR or MnR. Tracers were visualized by immunohistochemistry. In coronal sections, the different retrogradly labeled habenular neurons were quantified and assigned to the corresponding habenular subnuclei. Our results show that 1) the distribution of neurons in the LHb projecting to the three monoamine nuclei is similar and exhibits a great overlap, 2) the vast majority of LHb projection neurons target one monoaminergic nucleus only, and 3) very few, heterogeneously distributed LHb neurons project to both dopaminergic and serotonergic nuclei. These results imply that the LHb forms both separate and interconnected circuits with each monoaminergic nucleus, permitting the LHb to modulate its output to different monoamine systems either independently or jointly.

Lateral habenular neurons projecting to reward-processing monoaminergic nuclei express hyperpolarization-activated cyclic nucleotid-gated cation channels

The lateral habenular complex (LHb) is a key signal integrator between limbic forebrain regions and monoaminergic hindbrain nuclei. Major projections of LHb neurons target the dopaminergic ventral tegmental area (VTA) and the serotonergic dorsal (DR) and median raphe nuclei (MnR). Both monoaminergic neurotransmitter systems play a central role in reward processing and reward-related decision-making. Glutamatergic LHb efferents terminate on GABAergic neurons in the VTA, the rostromedial tegmental nucleus (RMTg), and the raphe nuclei, thereby suppressing monoamine release when required by the present behavioral context. Recent studies suggest that the LHb exerts a strong tonic inhibition on monoamine release when no reward is to be obtained. It is yet unknown whether this inhibition is the result of a continuous external activation by other brain areas, or if it is intrinsically generated by LHb projection neurons. To analyze whether the tonic inhibition may be the result of a hyperpolarization-activated cyclic nucleotid-gated cation channel (HCN)-mediated pacemaker activity of LHb projection neurons, we combined retrograde tracing in rats with in situ hybridization of HCN1 to HCN4 mRNAs. In fact, close to all LHb neurons targeting VTA or raphe nuclei are equipped with HCN subunit mRNAs. While HCN1 mRNA is scarce, most neurons display strong expression of HCN2 to HCN4 mRNAs, in line with the potential formation of heteromeric channels. These results are supported by quantitative PCR and immunocytochemical analyses. Thus, our data suggest that the tonic inhibition of monoamine release is intrinsically generated in LHb projection neurons and that their activity may only be modulated by synaptic inputs to the LHb.

Morphological and electrophysiological characteristics of neurons within identified subnuclei of the lateral habenula in rat brain slices

Based on the specificity of its inputs and targets, the lateral habenular complex (LHb) constitutes a pivotal motor-limbic interface implicated in various cerebral functions particularly in regulating monoamine transmission. Despite its functional significance, cellular characteristics underlying LHb functionality have not been examined systematically. The present study aimed to correlate morphological and electrophysiological properties of neurons within the different subnuclei of the LHb using whole-cell recording and neurobiotin labeling in rat slice preparations. Morphological analysis revealed a heterogeneous population of projection neurons randomly distributed throughout the LHb. According to somatodendritic characteristics four main categories were classified including spherical, fusiform, polymorphic and vertical cells. Electrophysiological characterization of neurons within the different categories demonstrated homologous profiles and no significant differences between groups. Typically, LHb neurons possessed high input resistances and long membrane time constants. They also displayed time-dependent inward rectification and distinct afterhyperpolarization. A salient electrophysiological feature of LHb neurons was their ability to generate rebound bursts of action potentials in response to membrane hyperpolarization. Based on the pattern of spontaneous activity, neurons were classified as silent, tonic or bursting. The occurrence of distinctive firing modes was not related to topographic allocation. The patterns of spontaneous firing and evoked discharge were highly sensitive to alterations in membrane potential and merged upon de- and hyperpolarizing current injection and synaptic stimulation. Besides projection neurons, recordings revealed the existence of a subpopulation of cells possessing morphological and physiological properties of neocortical neurogliaform cells. They were considered to be interneurons. Our data suggest that neurons within the different LHb subnuclei behave electrophysiologically more similar than expected, considering their morphological heterogeneity. We conclude that the formation of functional neuronal entities within the LHb may be achieved through defined synaptic inputs to particular neurons, rather than by individual neuronal morphologies and intrinsic membrane properties.

Glutamatergic axons from the lateral habenula mainly terminate on GABAergic neurons of the ventral midbrain

The concept of cortical-subcortical loops emphasizes the importance of the basal ganglia for motor, psychomotor, and emotional cortical functions. These loops are bidirectionally controlled by the midbrain dopaminergic system, predominantly but not exclusively at the level of the striatum including the accumbens nucleus. Successful behaviors increase the activities of the mesostriatal (arising in the complex part of the substantia nigra) and mesolimbic (arising in the ventral tegmental area, VTA) neurons, thereby reinforcing the corresponding actions. In contrast, unsuccessful behaviors result in an increased activation of the lateral habenular complex (LHb), thereby decreasing the activities of mesolimbic neurons. Correspondingly, electrical stimulation of the LHb effectively blocks neuronal activity in the VTA. Whether this block is due to an inhibitory projection from the LHb to the VTA, or whether axons from excitatory LHb neurons target inhibitory neurons within the VTA, is presently not known. Here we show, using in situ hybridization and immunocytochemical double labeling at the light and electron microscopic level, that GABAergic neurons are scarce in the LHb and that glutamatergic axons from the LHb mostly target GABAergic neurons in the VTA and the mesopontine rostromedial tegmental nucleus (RMTg), also known as tail of the VTA (tVTA). These data explain the inhibitory effect of LHb activation on the VTA. In addition, however, a small number of LHb terminals in the VTA actually contacts dopaminergic neurons. The biological importance of these terminals requires further investigation.

Dopaminergic activation excites rat lateral habenular neurons in vivo

The lateral habenular complex (LHb) of the epithalamus is part of a dorsal diencephalic conduction system connecting basal forebrain with regulatory midbrain nuclei. The LHb has been implicated in the regulation of ascending monoaminergic transmission, particularly midbrain dopaminergic neuronal activity. Here, we have investigated whether the LHb in turn is subject to dopaminergic modulation. Alterations in spontaneous neuronal activity within the LHb following systemic application of dopaminergic drugs have been examined in anesthetized rats using extracellular single unit recordings. The administration of apomorphine (2 mg/kg) resulted in an excitation of individual LHb neurons. On average, the spontaneous action potential firing of the LHb neurons was increased by 39%. However, the apomorphine effect showed marked topographic differences within the LHb. Particularly, a small subset of neurons in the lateral division of the LHb, which was localized within the oval subnucleus, showed an apomorphine-mediated increase in discharge frequency by 96%. In contrast, spontaneous discharge of neurons within other areas of the lateral division was not modified. Likewise, within the medial division of the LHb, a region that preferentially receives projections from dopaminergic midbrain nuclei, the majority of neurons failed to show apomorphine-mediated alterations in action potential firing. However, within the superior subnucleus of this division, an area with yet unclear afferent supply, spontaneous neuronal firing was enhanced by 56%. The apomorphine-mediated excitation of LHb neurons was antagonized by coapplication of haloperidol (2 mg/kg), which alone did not alter spontaneous action potential firing of individual LHb neurons. The present study demonstrates that spontaneous activity of distinct subsets of neurons within the LHb is strongly enhanced by systemic activation of dopaminergic receptors. Despite the small sample size, the data suggest that this dopaminergic modulation shows a topographic specificity. Therefore, the results support the hypothesis of a functional subnuclear organization of the rat habenular complex.

INVOLVEMENT OF THE HABENULAR COMPLEX IN THE COGNITIVE DEFICITS OF SCHIZOPHRENIA

The lateral habenular complex (LHb) is a key signal integrator between limbic forebrain regions and monoaminergic hindbrain nuclei. Major projections of LHb neurons target the dopaminergic ventral tegmental area (VTA) and the serotonergic dorsal (DR) and median raphe nuclei (MnR). Both monoaminergic neurotransmitter systems play a central role in reward processing and reward-related decision-making. Glutamatergic LHb efferents terminate on GABAergic neurons in the VTA, the rostromedial tegmental nucleus (RMTg), and the raphe nuclei, thereby suppressing monoamine release when required by the present behavioral context. Recent studies suggest that the LHb exerts a strong tonic inhibition on monoamine release when no reward is to be obtained. It is yet unknown whether this inhibition is the result of a continuous external activation by other brain areas, or if it is intrinsically generated by LHb projection neurons. To analyze whether the tonic inhibition may be the result of a hyperpolarization-activated cyclic nucleotid-gated cation channel (HCN)-mediated pacemaker activity of LHb projection neurons, we combined retrograde tracing in rats with in situ hybridization of HCN1 to HCN4 mRNAs. In fact, close to all LHb neurons targeting VTA or raphe nuclei are equipped with HCN subunit mRNAs. While HCN1 mRNA is scarce, most neurons display strong expression of HCN2 to HCN4 mRNAs, in line with the potential formation of heteromeric channels. These results are supported by quantitative PCR and immunocytochemical analyses. Thus, our data suggest that the tonic inhibition of monoamine release is intrinsically generated in LHb projection neurons and that their activity may only be modulated by synaptic inputs to the LHb.

Dopaminergic projections from the VTA substantially contribute to the mesohabenular pathway in the rat

Recent evidence suggests that the lateral habenular complex (LHb) is a source of negative reward signals in midbrain dopaminergic neurons. LHb activity, in turn, is modulated by locally released dopamine, which is largely derived from the ventral tegmental area (VTA) via the mesohabenular pathway. Unfortunately, the presumed importance of this modulation has not been appreciated so far, as its intensity had been largely underestimated in previous reports. Consequently, the present study used contemporary techniques to reexamine the origin of dopaminergic fibers to the LHb. For this purpose, the retrograde tract-tracer gold-coupled wheatgerm agglutinin was injected into the LHb of fourteen rats. Four of these animals providing the most representative information were selected for detailed analysis. In total, 343 retrogradely labeled neurons were detected in the VTAs of these animals. By far most of them were found in the anterior VTA, accumulating in its ventral paramedian fields. About 47% (162) of retrogradely labeled cells displayed tyrosine hydroxylase immunoreactivity, suggesting that almost half of the mesohabenular neurons are dopaminergic. In addition, our data suggest that also incerto-hypothalamic and periventricular neurons contribute dopaminergic terminals to the LHb. The majority of LHb neurons, however, does not project to the origin of the mesohabenular pathway in the anterior VTA. Consequently, there might be no closed VTA-LHb-VTA loop. Instead, our data are in line with the idea that the anterior VTA via its projection to the medial part of the LHb may modulate the information flow from the limbic forebrain to monoaminergic midbrain nuclei.

2019 Bifurcated projections of several structures in the forebrain to the bilateral lateral habenular nuclei in the wistar albino rat

Animal including human behavior is highly sophisticated. Besides reflective actions it is largely based on the desire for magnificent internal feelings, which are provided by the reward system. Its counterpart an “anti-reward” system is mainly composed of the lateral habenular complex (LHb) and its extensive interconnections with the monoaminergic cell groups in the mid- and hindbrain. The present review focuses on the neuronal composition and the internal signaling in the LHb. Morphologically six distinct types of neurons (spherical, fusiform-1, fusiform-2, polymorphic, vertical, neurogliaform) can be identified. In contrast, setting aside neurogliaform cells, only three broad categories (silent, tonic firing, bursting) can be identified using electrophysiological criteria. Functionally, LHb neurons express HCN channels and therefore in an “indifferent” situation LHb appears to be tonically active. When the situation takes a turn for the better habenular cells become inhibited, releasing dopaminergic VTA neurons from continuous damping. In contrast, when the situation takes a turn for the worse, LHb neurons are stimulated, completely shutting down the activity of dopaminergic cells in the VTA.

2017 Basal granular cells in the digestive epithelium of an ascidian

Animal including human behavior is highly sophisticated. Besides reflective actions it is largely based on the desire for magnificent internal feelings, which are provided by the reward system. Its counterpart an “anti-reward” system is mainly composed of the lateral habenular complex (LHb) and its extensive interconnections with the monoaminergic cell groups in the mid- and hindbrain. The present review focuses on the neuronal composition and the internal signaling in the LHb. Morphologically six distinct types of neurons (spherical, fusiform-1, fusiform-2, polymorphic, vertical, neurogliaform) can be identified. In contrast, setting aside neurogliaform cells, only three broad categories (silent, tonic firing, bursting) can be identified using electrophysiological criteria. Functionally, LHb neurons express HCN channels and therefore in an “indifferent” situation LHb appears to be tonically active. When the situation takes a turn for the better habenular cells become inhibited, releasing dopaminergic VTA neurons from continuous damping. In contrast, when the situation takes a turn for the worse, LHb neurons are stimulated, completely shutting down the activity of dopaminergic cells in the VTA.

Neuroanatomical tract tracing provides histological verification of neuron loss following cytotoxic lesions

In the present study we report a neuroanatomical procedure that provides direct histological verification of the extent of neuron loss following cytotoxic lesions of the lateral subdivision of the habenular complex (Lhb). Following kainic acid-induced lesions of Lhb neurons, the fluorescent retrograde tracer Fluoro-Gold was injected into the ventral midbrain where many medial habenula (Mhb) and Lhb neurons project. The absence of retrogradely labeled neurons in the Lhb indicated the extent of neuron loss there, and the presence of Fluoro-Gold-labeled neurons in the Mhb indicated that its neurons were intact. The extent of neuron loss in the Lhb was significantly correlated with behavioral data. Retrograde tract tracing can be used as an effective histological tool to verify the extent of neuron loss following a lesion procedure.