Functional opposition between habenula metabolism and the brain reward system

Shumake, Jason; González-Lima, Francisco

doi:10.3389/fnhum.2013.00662

Cited by 13 publications

(17 citation statements)

References 29 publications

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“…The habenula has recently attracted substantial interest due to the hypothesis that it may play an important role in certain symptoms of depression, such as low motivation. An extensive body of animal work supports this hypothesis, showing habenula hypermetabolism in rodent models of depression ( Shumake and Gonzalez-Lima, 2013 ; Dillon et al , 2014 ; Lecca et al , 2014 ; Proulx et al , 2014 ; Benarroch, 2015 ; Zhao et al , 2015 ). However, the relationship between habenula function and symptoms of depression in humans remains largely unclear.…”

Section: Introductionmentioning

confidence: 89%

Association between habenula dysfunction and motivational symptoms in unmedicated major depressive disorder

Liu

Valton

Wang

et al. 2017

Social Cognitive and Affective Neuroscience

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The lateral habenula plays a central role in reward and punishment processing and has been suggested to drive the cardinal symptom of anhedonia in depression. This hypothesis is largely based on observations of habenula hypermetabolism in animal models of depression, but the activity of habenula and its relationship with clinical symptoms in patients with depression remains unclear. High-resolution functional magnetic resonance imaging (fMRI) and computational modelling were used to investigate the activity of the habenula during a probabilistic reinforcement learning task with rewarding and punishing outcomes in 21 unmedicated patients with major depression and 17 healthy participants. High-resolution anatomical scans were also acquired to assess group differences in habenula volume. Healthy individuals displayed the expected activation in the left habenula during receipt of punishment and this pattern was confirmed in the computational analysis of prediction error processing. In depressed patients, there was a trend towards attenuated left habenula activation to punishment, while greater left habenula activation was associated with more severe depressive symptoms and anhedonia. We also identified greater habenula volume in patients with depression, which was associated with anhedonic symptoms. Habenula dysfunction may contribute to abnormal response to punishment in patients with depression, and symptoms such as anhedonia.

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Section: Introductionmentioning

confidence: 89%

Association between habenula dysfunction and motivational symptoms in unmedicated major depressive disorder

Liu

Valton

Wang

et al. 2017

Social Cognitive and Affective Neuroscience

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“…In agreement with these findings, increased LHb metabolism and reduced brain serotonin levels have been observed in several animal models of depression. This effect can be reversed with antidepressant drugs (Caldecott‐Hazard et al, ; Shumake and Gonzalez‐Lima, ) or lesions of the LHb (Yang et al, ). In fact, inactivation of the habenula by deep brain stimulation has been used in the treatment of major depressive disorder (Sartorius and Henn, ; Sartorius et al, ).…”

mentioning

confidence: 99%

Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates

Broms

Antolin-Fontes

Tingström

et al. 2014

J of Comparative Neurology

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The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, thus anatomically and functionally ideally positioned to regulate emotional, motivational and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G coupled-protein receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and Translating Ribosome Affinity Purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis we found that GPR151 expressing axons and terminals overlap with cholinergic, substance P-ergic and glutamatergic markers. Virtually identical expression pattern was observed in rat, mouse and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development.

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“…During the safety period, in both avoidance and escape, DA release in the NAc was increased (Oleson et al, 2012 ). Furthermore, brief electrical stimulation applied to the LHb contingent to the AA response (i.e., at the initiation of the safety period) impaired acquisition but not retention of 2WAA (Shumake et al, 2010 ; Ilango et al, 2013 ; Shumake and Gonzalez-Lima, 2013 ). Studies utilizing viral gene therapy in DA deficient mice showed that shock escape and learning 2WAA require DA signaling in both the amygdala and striatum.…”

Section: Role Of Motivational Circuitry In Aamentioning

confidence: 99%

Contribution of Emotional and Motivational Neurocircuitry to Cue-Signaled Active Avoidance Learning

Ilango

Shumake

Wetzel

et al. 2014

Front. Behav. Neurosci.

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Functional opposition between habenula metabolism and the brain reward system

Cited by 13 publications

References 29 publications

Association between habenula dysfunction and motivational symptoms in unmedicated major depressive disorder

Association between habenula dysfunction and motivational symptoms in unmedicated major depressive disorder

Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates

Contribution of Emotional and Motivational Neurocircuitry to Cue-Signaled Active Avoidance Learning

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