ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Dopamine D4 receptor excitation of lateral habenula neurons via multiple cellular mechanisms.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 90 citations in OpenAlex.
- PT320, a GLP-1 receptor agonist, mitigates nucleus accumbens-associated depression- and anxiety-like behaviors in MitoPark mice of Parkinson's disease.Journal of Parkinson's disease · 2026Article
- Effects of Repetitive Mild Traumatic Brain Injury on Corticotropin-Releasing Factor Modulation of Lateral Habenula Excitability and Motivated Behavior.Journal of neurotrauma · 2025Article
- Exploring Genetic and Receptor-Based Dopaminergic Strategies for Antidepressant Drug Development.Current gene therapy · 2025Review
- Effects of Repetitive Mild Traumatic Brain Injury on Corticotropin-Releasing Factor Modulation of Lateral Habenula Excitability and Motivated Behavior.bioRxiv : the preprint server for biology · 2024Article
- Whole-brain connections of glutamatergic neurons in the mouse lateral habenula in both sexes.Biology of sex differences · 2024Article
- Role of HCN channels in the functions of basal ganglia and Parkinson's disease.Cellular and molecular life sciences : CMLS · 2024Review
- Serotonergic Regulation of Synaptic Dopamine Levels Mitigates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- PT320, a Sustained-Release GLP-1 Receptor Agonist, Ameliorates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Effects of GABAResearch in pharmaceutical sciences · 2023Article
- The circadian clock in the mouse habenula is set by catecholamines.Cell and tissue research · 2022Article
- Multi-level variations of lateral habenula in depression: A comprehensive review of current evidence.Frontiers in psychiatry · 2022Review
- Acetaldehyde Excitation of Lateral Habenular Neurons via Multiple Cellular Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Heteromerization between αPharmacological research · 2021Article
- Sustained Release GLP-1 Agonist PT320 Delays Disease Progression in a Mouse Model of Parkinson's Disease.ACS pharmacology & translational science · 2021Article
- Entopeduncular Nucleus Projections to the Lateral Habenula Contribute to Cocaine Avoidance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Inhibition Within the Lateral Habenula-Implications for Affective Disorders.Frontiers in behavioral neuroscience · 2021Review
- Early life stress dysregulates kappa opioid receptor signaling within the lateral habenula.Neurobiology of stress · 2020Article
- Delayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice.International journal of molecular sciences · 2019Article
- Release parameters during progressive degeneration of dopamine neurons in a mouse model reveal earlier impairment of spontaneous than forced behaviors.Journal of neurochemistry · 2019Article
- Dopamine DJournal of medicinal chemistry · 2019Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutamatergic lateral habenula (LHb) output communicates negative motivational valence to ventral tegmental area (VTA) dopamine (DA) neurons via activation of the rostromedial tegmental nucleus (RMTg). However, the LHb also receives a poorly understood DA input from the VTA, which we hypothesized constitutes an important feedback loop regulating DA responses to stimuli. Using whole-cell electrophysiology in rat brain slices, we find that DA initiates a depolarizing inward current (I(DAi)) and increases spontaneous firing in 32% of LHb neurons. I(DAi) was also observed upon application of amphetamine or the DA uptake blockers cocaine or GBR12935, indicating involvement of endogenous DA. I(DAi) was blocked by D4 receptor (D4R) antagonists (L745,870 or L741,742), and mimicked by a selective D4R agonist (A412997). I(DAi) was associated with increased whole-cell conductance and was blocked by Cs+ or a selective blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel, ZD7288. I(DAi) was also associated with a depolarizing shift in half-activation voltage for the hyperpolarization-activated cation current (Ih) mediated by HCN channels. Recordings from LHb neurons containing fluorescent retrograde tracers revealed that I(DAi) was observed only in cells projecting to the RMTg and not the VTA. In parallel with direct depolarization, DA also strongly increased synaptic glutamate release and reduced synaptic GABA release onto LHb cells. These results demonstrate that DA can excite glutamatergic LHb output to RMTg via multiple cellular mechanisms. Since the RMTg strongly inhibits midbrain DA neurons, activation of LHb output to RMTg by DA represents a negative feedback loop that may dampen DA neuron output following activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.