Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin.

ABSTRACT: The lateral habenula (LHb) has recently been identified as a key regulator of the reward system by driving inhibition onto dopaminergic neurons. However, the nature and potential modulation of the major input to the LHb originating from the basal ganglia are poorly understood. Although the output of the basal ganglia is thought to be primarily inhibitory, here we show that transmission from the basal ganglia to the LHb is excitatory, glutamatergic, and suppressed by serotonin. Behaviorally, activation of this pathway is aversive, consistent with its role as an "antireward" signal. Our demonstration of an excitatory projection from the basal ganglia to the LHb explains how LHb-projecting basal ganglia neurons can have similar encoding properties as LHb neurons themselves. Our results also provide a link between antireward excitatory synapses and serotonin, a neuromodulator implicated in depression.

SUBMITTER: Shabel SJ

PROVIDER: S-EPMC3471532 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin.

Shabel Steven J SJ Proulx Christophe D CD Trias Anthony A Murphy Ryan T RT Malinow Roberto R

Neuron 20120501 3

The lateral habenula (LHb) has recently been identified as a key regulator of the reward system by driving inhibition onto dopaminergic neurons. However, the nature and potential modulation of the major input to the LHb originating from the basal ganglia are poorly understood. Although the output of the basal ganglia is thought to be primarily inhibitory, here we show that transmission from the basal ganglia to the LHb is excitatory, glutamatergic, and suppressed by serotonin. Behaviorally, acti ...[more]

PMID: 22578499

Similar Datasets

Lateral Habenula determines long-term storage of aversive memories.

Project description:The Lateral Habenula (LHb) is a small brain structure that codifies negative motivational value and has been related to major depression. It has been shown recently that LHb activation is sufficient to induce aversive associative learning; however the key question about whether LHb activation is required for an aversive memory to be formed has not been addressed. In this article we studied the function of the LHb in memory formation using the Inhibitory Avoidance task (IA). We found that LHb inactivation during IA training does not disrupt memory when assessed 24 h after, but abolishes it 7 days later, indicating that LHb activity during memory acquisition is not necessary for memory formation, but regulates its temporal stability. These effects suggest that LHb inactivation modifies subjective perception of the training experience.

| S-EPMC4026688 | biostudies-literature

Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation.

Project description:The lateral habenula has been widely studied for its contribution in generating reward-related behaviors [1, 2]. We have found that this nucleus plays an unexpected role in the sedative actions of the general anesthetic propofol. The lateral habenula is a glutamatergic, excitatory hub that projects to multiple targets throughout the brain, including GABAergic and aminergic nuclei that control arousal [3-5]. When glutamate release from the lateral habenula in mice was genetically blocked, the ability of propofol to induce sedation was greatly diminished. In addition to this reduced sensitivity to propofol, blocking output from the lateral habenula caused natural non-rapid eye movement (NREM) sleep to become highly fragmented, especially during the rest ("lights on") period. This fragmentation was largely reversed by the dual orexinergic antagonist almorexant. We conclude that the glutamatergic output from the lateral habenula is permissive for the sedative actions of propofol and is also necessary for the consolidation of natural sleep.

| S-EPMC5835141 | biostudies-literature

Dynamic input-dependent encoding of individual basal ganglia neurons.

Project description:Computational models are crucial to studying the encoding of individual neurons. Static models are composed of a fixed set of parameters, thus resulting in static encoding properties that do not change under different inputs. Here, we challenge this basic concept which underlies these models. Using generalized linear models, we quantify the encoding and information processing properties of basal ganglia neurons recorded in-vitro. These properties are highly sensitive to the internal state of the neuron due to factors such as dependency on the baseline firing rate. Verification of these experimental results with simulations provides insights into the mechanisms underlying this input-dependent encoding. Thus, static models, which are not context dependent, represent only part of the neuronal encoding capabilities, and are not sufficient to represent the dynamics of a neuron over varying inputs. Input-dependent encoding is crucial for expanding our understanding of neuronal behavior in health and disease and underscores the need for a new generation of dynamic neuronal models.

| S-EPMC7118110 | biostudies-literature

Serotonin modulates glutamatergic transmission to neurons in the lateral habenula.

Project description:The lateral habenula (LHb) is bilaterally connected with serotoninergic raphe nuclei, and expresses high density of serotonin receptors. However, actions of serotonin on the excitatory synaptic transmission to LHb neurons have not been thoroughly investigated. The LHb contains two anatomically and functionally distinct regions: lateral (LHbl) and medial (LHbm) divisions. We compared serotonin's effects on glutamatergic transmission across the LHb in rat brains. Serotonin bi-directionally and differentially modulated glutamatergic transmission. Serotonin inhibited glutamatergic transmission in higher percentage of LHbl neurons but potentiated in higher percentage of LHbm neurons. Magnitude of potentiation was greater in LHbm than in LHbl. Type 2 and 3 serotonin receptor antagonists attenuated serotonin's potentiation. The serotonin reuptake blocker, and the type 2 and 3 receptor agonists facilitated glutamatergic transmission in both LHbl and LHbm neurons. Thus, serotonin via activating its type 2, 3 receptors, increased glutamate release at nerve terminals in some LHb neurons. Our data demonstrated that serotonin affects both LHbm and LHbl. Serotonin might play an important role in processing information between the LHb and its downstream-targeted structures during decision-making. It may also contribute to a homeostatic balance underlying the neural circuitry between the LHb and raphe nuclei.

| S-EPMC4817146 | biostudies-other

Predominant Striatal Input to the Lateral Habenula in Macaques Comes from Striosomes.

Project description:Striosomes, neurochemically specialized modules in the striatum, are thought to be nodes in circuits extending, via basal ganglia pathways, from mood-related neocortical regions to dopamine-containing neurons of the substantia nigra. Yet striosomes have remained beyond the reach of electrophysiological methods to identify them, especially in non-human primates. Such work is needed for translational as well as for basic science. Here we introduce a method to identify striosomes on-line in awake, behaving macaques. We combined electrical microstimulation of the striatum with simultaneous electrophysiological recording in the lateral habenula (LHb) followed by immunohistochemistry. We demonstrate that striosomes provide the predominant striatal input to the macaque pallido-habenular circuit, which is known to function in relation to reinforcement signaling. Further, our experiments suggest that striosomes from different striatal regions may convergently influence the lateral habenula. This work now opens the way to defining the functions of striosomes in behaving primates in relation to mood, motivation, and action.

| S-EPMC6561345 | biostudies-literature

mGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output.

Project description:Excitatory and inhibitory transmission onto lateral habenula (LHb) neurons is instrumental for the expression of positive and negative motivational states. However, insights into the molecular mechanisms modulating synaptic transmission and the repercussions for neuronal activity within the LHb remain elusive. Here, we report that, in mice, activation of group I metabotropic glutamate receptors triggers long-term depression at excitatory (eLTD) and inhibitory (iLTD) synapses in the LHb. mGluR-eLTD and iLTD rely on mGluR1 and PKC signaling. However, mGluR-dependent adaptations of excitatory and inhibitory synaptic transmission differ in their expression mechanisms. mGluR-eLTD occurs via an endocannabinoid receptor-dependent decrease in glutamate release. Conversely, mGluR-iLTD occurs postsynaptically through PKC-dependent reduction of β2-containing GABAA-R function. Finally, mGluR-dependent plasticity of excitation or inhibition decides the direction of neuronal firing, providing a synaptic mechanism to bidirectionally control LHb output. We propose mGluR-LTD as a cellular substrate that underlies LHb-dependent encoding of opposing motivational states.

| S-EPMC5009114 | biostudies-literature

Esr1+ hypothalamic-habenula neurons shape aversive states

Project description: Not available

| S-BSST1069 | biostudies-other

Excitatory Transmission to the Lateral Habenula Is Critical for Encoding and Retrieval of Spatial Memory.

Project description:The lateral habenula (LHb) is viewed as a relay between the limbic system, the basal ganglia (BG), and monoaminergic neurons of the midbrain. If a prominent role has been evidenced in BG-mediated functions such as value-based decision-making, very little is known about the involvement of the LHb in limbic functions such as memory processing. In the present study, we used two pharmacological approaches-LHb reversible inactivation with intra-LHb infusion of muscimol, an agonist of the GABA-A receptor, or blockade of excitatory inputs with intra-LHb infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of the glutamatergic AMPA receptor-to investigate the involvement of the LHb in encoding, consolidation, and retrieval of spatial memory in the water maze (WM) in rats. We found that intra-LHb infusion of muscimol or CNQX prevented encoding and retrieval, but not consolidation of spatial information. In addition, muscimol but not CNQX induced impairments during a cued version of the WM task, and marked anxiety in the elevated plus maze. These results confirm the involvement of the LHb in higher cognitive functions. They further suggest a dichotomy between the role of glutamatergic and other inputs to the LHb in hippocampus-dependent memory processing, as well as in emotional aspects of goal-directed behaviors.

| S-EPMC4864662 | biostudies-literature

1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis.

Project description:Previous studies have evaluated motor and extramotor cerebral cortical regions in patients with amyotrophic lateral sclerosis (ALS) using (1) H MRS, but none have evaluated the thalamus or basal ganglia. The objective of this exploratory study was to evaluate the subclinical involvement of the basal ganglia and thalamus in patients with ALS using (1) H MRS. Fourteen patients (52±7 years) with sporadic definite ALS and 17 age-matched controls were studied using volumetric MRSI on a 3-T scanner. The concentration of the metabolites N-acetylaspartate (NAA), choline (Cho) and their ratio (NAA/Cho) were obtained bilaterally from the basal ganglia (lentiform nucleus, caudate) and thalamus. The maximum rates of finger and foot tap and lip and tongue movements were obtained to assess extrapyramidal and pyramidal tract function. In patients with ALS, relative to controls, the NAA concentration was significantly lower (p<0.02) in the basal ganglia and thalamus, and the Cho concentration was higher (p<0.01) in these structures, except in the caudate (p=0.04). Correspondingly, the NAA/Cho ratio was significantly lower (p<0.01) in these structures, except in the caudate (p=0.03), in patients than in controls. There were mild to strong correlations (r=0.4-0.7) between the metabolites of the basal ganglia and finger tap, foot tap and lip and tongue movement rates. In conclusion, decreased NAA in the basal ganglia and thalamus and increased Cho and decreased NAA/Cho in the lentiform nucleus and thalamus are indicative of neuronal loss or dysfunction and alterations in choline-containing membranes in these structures.

| S-EPMC3210902 | biostudies-other

Activation of basal forebrain-to-lateral habenula circuitry drives reflexive aversion and suppresses feeding behavior.

Project description:Environmental cues and internal states such as mood, reward, or aversion directly influence feeding behaviors beyond homeostatic necessity. The hypothalamus has been extensively investigated for its role in homeostatic feeding. However, many of the neural circuits that drive more complex, non-homeostatic feeding that integrate valence and sensory cues (such as taste and smell) remain unknown. Here, we describe a basal forebrain (BF)-to-lateral habenula (LHb) circuit that directly modulates non-homeostatic feeding behavior. Using viral-mediated circuit mapping, we identified a population of glutamatergic neurons within the BF that project to the LHb, which responds to diverse sensory cues, including aversive and food-related odors. Optogenetic activation of BF-to-LHb circuitry drives robust, reflexive-like aversion. Furthermore, activation of this circuitry suppresses the drive to eat in a fasted state. Together, these data reveal a role of basal forebrain glutamatergic neurons in modulating LHb-associated aversion and feeding behaviors by sensing environmental cues.

| S-EPMC9772215 | biostudies-literature

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