Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance.

ABSTRACT: Lateral habenula (LHb) projections to the ventral midbrain, including the rostromedial tegmental nucleus (RMTg), convey negative reward-related information, but the behavioral ramifications of selective activation of this pathway remain unexplored. We found that exposure to aversive stimuli in mice increased LHb excitatory drive onto RMTg neurons. Furthermore, optogenetic activation of this pathway promoted active, passive and conditioned behavioral avoidance. Thus, activity of LHb efferents to the midbrain is aversive but can also serve to negatively reinforce behavioral responding.

SUBMITTER: Stamatakis AM

PROVIDER: S-EPMC3411914 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance.

Stamatakis Alice M AM Stuber Garret D GD

Nature neuroscience 20120624 8

Lateral habenula (LHb) projections to the ventral midbrain, including the rostromedial tegmental nucleus (RMTg), convey negative reward-related information, but the behavioral ramifications of selective activation of this pathway remain unexplored. We found that exposure to aversive stimuli in mice increased LHb excitatory drive onto RMTg neurons. Furthermore, optogenetic activation of this pathway promoted active, passive and conditioned behavioral avoidance. Thus, activity of LHb efferents to ...[more]

PMID: 22729176

Similar Datasets

Sexual Dimorphism of Inputs to the Lateral Habenula in Mice.

Project description:The lateral habenula (LHb), which is a critical neuroanatomical hub and a regulator of midbrain monoaminergic centers, is activated by events resulting in negative valence and contributes to the expression of both appetitive and aversive behaviors. However, whole-brain cell-type-specific monosynaptic inputs to the LHb in both sexes remain incompletely elucidated. In this study, we used viral tracing combined with in situ hybridization targeting vesicular glutamate transporter 2 (vGlut2) and glutamic acid decarboxylase 2 (Gad2) to generate a comprehensive whole-brain atlas of inputs to glutamatergic and γ-aminobutyric acid (GABA)ergic neurons in the LHb. We found >30 ipsilateral and contralateral brain regions that projected to the LHb. Of these, there were significantly more monosynaptic LHb-projecting neurons from the lateral septum, anterior hypothalamus, dorsomedial hypothalamus, and ventromedial hypothalamus in females than in males. More interestingly, we found a stronger GABAergic projection from the medial septum to the LHb in males than in females. Our results reveal a comprehensive connectivity atlas of glutamatergic and GABAergic inputs to the LHb in both sexes, which may facilitate a better understanding of sexual dimorphism in physiological and pathological brain functions.

| S-EPMC9723051 | biostudies-literature

Identification of the zebrafish ventral habenula as a homolog of the mammalian lateral habenula.

Project description:The mammalian habenula consists of the medial and lateral habenulae. Recent behavioral and electrophysiological studies suggested that the lateral habenula plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopaminergic and serotonergic neurons. Despite the functional significance, manipulating neural activity in this pathway remains difficult because of the absence of a genetically accessible animal model such as zebrafish. To address the level of lateral habenula conservation in zebrafish, we applied the tract-tracing technique to GFP (green fluorescent protein)-expressing transgenic zebrafish to identify habenular neurons that project to the raphe nuclei, a major target of the mammalian lateral habenula. Axonal tracing in live and fixed fish showed projection of zebrafish ventral habenula axons to the ventral part of the median raphe, but not to the interpeduncular nucleus where the dorsal habenula projected. The ventral habenula expressed protocadherin 10a, a specific marker of the rat lateral habenula, whereas the dorsal habenula showed no such expression. Gene expression analyses revealed that the ventromedially positioned ventral habenula in the adult originated from the region of primordium lateral to the dorsal habenula during development. This suggested that zebrafish habenulae emerge during development with mediolateral orientation similar to that of the mammalian medial and lateral habenulae. These findings indicated that the lateral habenular pathways are evolutionarily conserved pathways and might control adaptive behaviors in vertebrates through the regulation of monoaminergic activities.

| S-EPMC6633804 | biostudies-literature

Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation.

Project description:Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic component of the LH-VTA pathway supports positive reinforcement and place preference, while the glutamatergic component mediates place avoidance. In addition, our results indicate that photoactivation of these projections modulates other behaviors, such as social interaction and perseverant investigation of a novel object. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activation across multiple contexts, consistent with a role in increasing motivational salience. VIDEO ABSTRACT.

| S-EPMC4961212 | biostudies-literature

Activation of the Lateral Habenula-Ventral Tegmental Area Neural Circuit Contributes to Postoperative Cognitive Dysfunction in Mice.

Project description:Postoperative cognitive dysfunction (POCD) is common and is associated with poor outcome. Neural circuit involvement in POCD is unknown. Lateral habenula (LHb) that regulates coping and depression-like behaviors after aversive stimuli is activated by surgery in the previous study. Here, surgery activated LHb and ventral tegmental area (VTA) are presented. VTA is known to receive projections from LHb and project to the prefrontal cortex and hippocampus. Direct chemogenetic inhibition of LHb or damaging LHb attenuates surgery-induced learning and memory impairment, N-methyl-d-aspartate (NMDA) receptor activation, endoplasmic reticulum stress, inflammatory responses and cell injury in the VTA, and activation of rostromedial tegmental nucleus, an intermediate station to connect LHb with VTA. LHb inhibition preserves dendritic spine density in the prefrontal cortex and hippocampus. Retrograde inhibition of LHb via its projections to VTA attenuated surgery-induced learning and memory dysfunction is observed. Retrograde activation of LHb induced learning and memory dysfunction is observed. Inhibition of NMDA receptors, dopamine synthesis, and endoplasmic reticulum stress in the VTA reduced surgery-induced learning and memory impairment, inflammatory responses, and cell injury are observed. These results suggest that surgery activates the LHb-VTA neural circuit, which contributes to POCD and neuropathological changes in the brain. These novel findings represent initial evidence for neural circuit involvement in surgery effects.

| S-EPMC9353455 | biostudies-literature

Parallel ventral hippocampus-lateral septum pathways differentially regulate approach-avoidance conflict.

Project description:The ability to resolve an approach-avoidance conflict is critical to adaptive behavior. The ventral CA3 (vCA3) and CA1 (vCA1) subfields of the ventral hippocampus (vHPC) have been shown to facilitate avoidance and approach behavior, respectively, in the face of motivational conflict, but the neural circuits by which this subfield-specific regulation is implemented is unknown. We demonstrate that two distinct pathways from these subfields to lateral septum (LS) contribute to this divergent control. In Long-Evans rats, chemogenetic inhibition of the vCA3- LS caudodorsal (cd) pathway potentiated approach towards a learned conflict-eliciting stimulus, while inhibition of the vCA1-LS rostroventral (rv) pathway potentiated approach non-specifically. Additionally, vCA3-LScd inhibited animals were less hesitant to explore food during environmental uncertainty, while the vCA1- LSrv inhibited animals took longer to initiate food exploration. These findings suggest that the vHPC influences multiple behavioral systems via differential projections to the LS, which in turn send inhibitory projections to motivational centres of the brain.

| S-EPMC9187740 | biostudies-literature

Transcriptional and functional divergence in lateral hypothalamic glutamate neurons projecting to the lateral habenula and ventral tegmental area.

Project description:The lateral hypothalamic area (LHA) regulates feeding- and reward-related behavior, but because of its molecular and anatomical heterogeneity, the functions of defined neuronal populations are largely unclear. Glutamatergic neurons within the LHA (LHAVglut2) negatively regulate feeding and appetitive behavior. However, this population comprises transcriptionally distinct and functionally diverse neurons that project to diverse brain regions, including the lateral habenula (LHb) and ventral tegmental area (VTA). To resolve the function of distinct LHAVglut2 populations, we systematically compared projections to the LHb and VTA using viral tracing, single-cell sequencing, electrophysiology, and in vivo calcium imaging. LHAVglut2 neurons projecting to the LHb or VTA are anatomically, transcriptionally, electrophysiologically, and functionally distinct. While both populations encode appetitive and aversive stimuli, LHb projecting neurons are especially sensitive to satiety state and feeding hormones. These data illuminate the functional heterogeneity of LHAVglut2 neurons, suggesting that reward and aversion are differentially processed in divergent efferent pathways.

| S-EPMC8812999 | biostudies-literature

A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward.

Project description:Lateral habenula (LHb) neurons convey aversive and negative reward conditions through potent indirect inhibition of ventral tegmental area (VTA) dopaminergic neurons. Although VTA dopaminergic neurons reciprocally project to the LHb, the electrophysiological properties and the behavioral consequences associated with selective manipulations of this circuit are unknown. Here, we identify an inhibitory input to the LHb arising from a unique population of VTA neurons expressing dopaminergic markers. Optogenetic activation of this circuit resulted in no detectable dopamine release in LHb brain slices. Instead, stimulation produced GABA-mediated inhibitory synaptic transmission, which suppressed the firing of postsynaptic LHb neurons in brain slices and increased the spontaneous firing rate of VTA dopaminergic neurons in vivo. Furthermore, in vivo activation of this pathway produced reward-related phenotypes that were dependent on intra-LHb GABAA receptor signaling. These results suggest that noncanonical inhibitory signaling by these hybrid dopaminergic-GABAergic neurons act to suppress LHb output under rewarding conditions.

| S-EPMC3873746 | biostudies-other

A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling.

Project description:The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ER?) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2. This cell type is anatomically located to receive afferents from midbrain reward (dopamine and serotonin) and hypothalamic water and energy homeostasis (vasopressin and orexin) circuits. These afferents shared the expression of estrogen synthase (aromatase) and VGLUT2, both in their somata and axon terminals. We demonstrate dynamic changes in LHbM VGAT+ cell density, dependent upon gonadal functional status, that closely correlate with motivational behavior in response to predator and forced swim stressors. The findings suggest that the homeostasis and reward-related glutamatergic convergent projecting pathways to LHbMC employ a localized neurosteroid signaling mechanism via axonal expression of aromatase, to act as a switch for GERN excitation/inhibition output prevalence, influencing depressive or motivated behavior.

| S-EPMC5865187 | biostudies-literature

Ventral hippocampus-lateral septum circuitry promotes foraging-related memory.

Project description:Remembering the location of a food or water source is essential for survival. Here, we reveal that spatial memory for food location is reflected in ventral hippocampus (HPCv) neuron activity and is impaired by HPCv lesion. HPCv mediation of foraging-related memory involves communication to the lateral septum (LS), as either reversible or chronic disconnection of HPCv-to-LS signaling impairs spatial memory retention for food or water location. This neural pathway selectively encodes appetitive spatial memory, as HPCv-LS disconnection does not affect spatial memory for escape location in a negative reinforcement procedure, food intake, or social and olfactory-based appetitive learning. Neural pathway tracing and functional mapping analyses reveal that LS neurons recruited during the appetitive spatial memory procedure are primarily GABAergic neurons that project to the lateral hypothalamus. Collective results emphasize that the neural substrates controlling spatial memory are outcome specific based on reinforcer modality.

| S-EPMC9605732 | biostudies-literature

Mapping genotype-expression associations in Heterogeneous Stock rat brains to advance behavioral genetics research [Lateral habenula]

Project description:Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.

2021-04-23 | GSE173138 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data