The role of the basal ganglia in motivated behavior

Cunha, Cláudio Da; Gómez-A, Alexander; Blaha, Charles D.

doi:10.1515/revneuro-2012-0063

Cited by 48 publications

(45 citation statements)

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“…A growing body of evidence has shown that the BG forms a neural network dedicated to selection (Nicola, 2007; Redgrave et al, 2008, 2010; Da Cunha et al, 2009, 2012; Grillner et al, 2013). The strongest evidence is related to action-selection by the cortico-BG motor loop (Frank and Claus, 2006; Frank, 2011; Isoda and Hikosaka, 2011; Mink, 1996; Mogenson et al, 1980).…”

Section: Bg Cortico-thalamic Loopmentioning

confidence: 99%

“…The BG has been proposed as a system to make selections: action-selection, reasoning/cognition related selections, and motivational state selections (Da Cunha et al, 2009, 2012; Redgrave et al, 2011). Understanding how the cortico-BG circuitry is suited for such computations is critical to understand how electrical stimulation of parts of this system can improve and/or motor and psychicatric functions.…”

Section: Introductionmentioning

confidence: 99%

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Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

Cunha

Boschen

Gómez-A

et al. 2015

Neuroscience & Biobehavioral Reviews

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This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.

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Section: Bg Cortico-thalamic Loopmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

Cunha

Boschen

Gómez-A

et al. 2015

Neuroscience & Biobehavioral Reviews

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“…It includes DA neurons of the ventral tegmental area (VTA), projecting to prefrontal cortex (PFC) and limbic areas (e.g., ventral striatum), and DA neurons of the substantia nigra (SN), projecting to the dorsal striatum (6). Involvement of the midbrain DA system is strongly implicated in both the cognitive and motivational deficits observed in schizophrenia (7,8). Moreover, it is well documented that the DA system is altered in patients with schizophrenia (reviewed in refs.…”

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confidence: 99%

Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area

Krabbe

Duda

Schiemann

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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There is strong evidence that the core deficits of schizophrenia result from dysfunction of the dopamine (DA) system, but details of this dysfunction remain unclear. We previously reported a model of transgenic mice that selectively and reversibly overexpress DA D2 receptors (D2Rs) in the striatum (D2R-OE mice). D2R-OE mice display deficits in cognition and motivation that are strikingly similar to the deficits in cognition and motivation observed in patients with schizophrenia. Here, we show that in vivo, both the firing rate (tonic activity) and burst firing (phasic activity) of identified midbrain DA neurons are impaired in the ventral tegmental area (VTA), but not in the substantia nigra (SN), of D2R-OE mice. Normalizing striatal D2R activity by switching off the transgene in adulthood recovered the reduction in tonic activity of VTA DA neurons, which is concordant with the rescue in motivation that we previously reported in our model. On the other hand, the reduction in burst activity was not rescued, which may be reflected in the observed persistence of cognitive deficits in D2R-OE mice. We have identified a potential molecular mechanism for the altered activity of DA VTA neurons in D2R-OE mice: a reduction in the expression of distinct NMDA receptor subunits selectively in identified mesolimbic DA VTA, but not nigrostriatal DA SN, neurons. These results suggest that functional deficits relevant for schizophrenia symptoms may involve differential regulation of selective DA pathways.ventral tegmental area | dopamine D2 receptor | burst activity | NMDA receptor | schizophrenia D eficits in cognition and motivation are core features of schizophrenia (1, 2). These symptoms are listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as a diagnostic criterion for schizophrenia spectrum disorder (3) and have a significant impact on patients' overall functioning and quality of life (4, 5). Currently, there are no effective treatments for these disabling aspects of the disease. Therefore, a high priority in the study of schizophrenia is to increase our understanding of the neurobiology of cognitive and motivational deficits. The midbrain dopamine (DA) system affects cognition and motivation in healthy subjects. It includes DA neurons of the ventral tegmental area (VTA), projecting to prefrontal cortex (PFC) and limbic areas (e.g., ventral striatum), and DA neurons of the substantia nigra (SN), projecting to the dorsal striatum (6). Involvement of the midbrain DA system is strongly implicated in both the cognitive and motivational deficits observed in schizophrenia (7,8). Moreover, it is well documented that the DA system is altered in patients with schizophrenia (reviewed in refs. 9, 10).To model the increase in striatal DA D2 receptor (D2R) activity observed in patients with schizophrenia, we previously generated transgenic mice that selectively and reversibly overexpress D2Rs in the striatum (D2R-OE mice) (11). In this model, expression of the transgenic D2Rs is restricted to the postsy...

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“…The striatum occupies a central role in signal attenuation throughout the basal ganglia circuitry that is involved in cognition, emotional processes, and motor responses. Several recent review articles detail the intricacies of this brain region [36][37][38][39][40]. It has been hypothesized that two main circuits signal from the striatum: (1) the striatopallidal/indirect pathway and (2) the striatonigral/direct pathway.…”

Section: Circuitrymentioning

confidence: 99%

The Use of PDE10A and PDE9 Inhibitors for Treating Schizophrenia

Tuttle

Kormos

2014

Small Molecule Therapeutics for Schizophrenia

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Schizophrenia (Scz) is a chronic and debilitating neurological disorder that afflicts approximately 1% of the general population with an increased incidence within families. Signs of this disorder typically appear between the ages of 16-30 although rare cases of childhood (<13) onset exist. Diagnosis of scz requires symptoms that persist for a duration of 1 month over a 6-month time period. The broad spectrum of symptoms are typically split into three categories: positive, negative, and cognitive. Implicit within these categories is the difficulty for stand-alone treatment methods, suggesting a combination of pharmacological and psychological treatment strategies is needed to manage this disease. Furthermore, while current pharmaceuticals are moderately effective at managing positive symptoms, the severe side effects lower patient compliance. Additionally, drugs used to treat negative and cognitive symptoms only have modest benefits, at best. Due to these limitations, there is a clear need for novel pharmaceuticals that modulate dysfunctional neurological pathways in scz patients. As such, both academic and pharmaceutical researchers are focused on identifying enzymes that can attenuate neurological signaling in disease-relevant brain regions. Specifically, this chapter will provide an in-depth review of current drug discovery efforts focused on inhibiting phosphodiesterase 10 and 9 (PDE10A, PDE9A, respectively).

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The role of the basal ganglia in motivated behavior

Cited by 48 publications

References 0 publications

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area

The Use of PDE10A and PDE9 Inhibitors for Treating Schizophrenia

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