scholarly journals Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rafael Renteria ◽  
Christian Cazares ◽  
Emily T Baltz ◽  
Drew C Schreiner ◽  
Ege A Yalcinbas ◽  
...  
Keyword(s):  
Decision Making ◽  
Dorsal Striatum ◽  
Alcohol Exposure ◽  
Psychiatric Disease ◽  
Projection Neurons ◽  
Orbital Frontal Cortex ◽  
Underlying Mechanisms ◽  
Reduced Activity

Psychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyper-activity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively, however, the underlying mechanisms are unknown. Here we show that alcohol exposed mice have enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid (eCB) signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation specific mechanism gating OFC activity in alcohol exposed mice.

scholarly journals Mechanism for differential recruitment of orbitostriatal transmission during outcomes and actions in alcohol dependence

2020 ◽  
Author(s):  
Rafael Renteria ◽  
Christian Cazares ◽  
Emily T. Baltz ◽  
Drew C. Schreiner ◽  
Ege A. Yalcinbas ◽  
...  
Keyword(s):  
Decision Making ◽  
Alcohol Dependence ◽  
Dorsal Striatum ◽  
Psychiatric Disease ◽  
Projection Neurons ◽  
Orbital Frontal Cortex ◽  
Underlying Mechanisms ◽  
Reduced Activity

AbstractPsychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyper-activity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively, however, the underlying mechanisms are unknown. Here we show that alcohol dependence enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid (eCB) signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation specific mechanism gating OFC activity following the induction of alcohol dependence.

scholarly journals Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

2018 ◽  
Author(s):  
Christian R. Lee ◽  
Alex J. Yonk ◽  
Joost Wiskerke ◽  
Kenneth G. Paradiso ◽  
James M. Tepper ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Dorsal Striatum ◽  
Behavioral Effect ◽  
Projection Neurons ◽  
Cortical Input ◽  
Optogenetic Stimulation ◽  
Main Input ◽  
Opposing Effects ◽  
Stimulation Of

SummaryThe striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

scholarly journals Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioural and [18F]JNJ42259152 PET study in rats

2021 ◽  
Author(s):  
Bart de Laat ◽  
Yvonne E. Klingl ◽  
Gwen Schroyen ◽  
Maarten Ooms ◽  
Jacob M Hooker ◽  
...  
Keyword(s):  
Decision Making ◽  
Alcohol Consumption ◽  
Alcohol Intake ◽  
Iowa Gambling Task ◽  
Alcohol Exposure ◽  
Alcohol Preference ◽  
Binding Potential ◽  
Reference Tissue ◽  
Volume Of Interest

Abstract Purpose Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety. Methods We performed a longitudinal [18F]JNJ42259152 microPET study to evaluate PDE10A changes over a 9-week intermittent access to alcohol model, including 6 weeks of alcohol exposure, 2 weeks of abstinence followed by 1 week relapse. Parametric PDE10A binding potential (BPND) images were generated using a Logan reference tissue model with cerebellum as reference region and were analyzed using both a volume-of-interest and voxel-based approach. Moreover, individual decision-making and anxiety levels were assessed with the rat Iowa Gambling Task and open field test over the IAE model. Results We observed an increased alcohol preference especially in those animals that exhibited poor initial decision-making. The first 2-weeks of alcohol exposure resulted in an increased striatal PDE10A binding (> 10%). Comparing PDE10A binding potential after 2- versus 4-weeks of exposure, showed a significant decreased PDE10A in the caudate-putamen and nucleus accumbens (pFWEcorrected<0.05). This striatal PDE10A decrease was related to alcohol consumption and preference. Normalization of striatal PDE10A to initial levels was observed after 1 week of relapse, apart from the globus pallidus. Conclusion This study shows that chronic voluntary alcohol consumption induces a reversible increased PDE10A enzymatic availability in the striatum, which is related to the amount of alcohol preference. Thus, PDE10A-mediated signaling plays an important role in modulating the reinforcing effects of alcohol, and the data suggest that PDE10A inhibition may have beneficial behavioral effects on alcohol intake.

scholarly journals Cell type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons

2021 ◽  
Author(s):  
Benoit Forget ◽  
Elena Martin Garcia ◽  
Arthur Godino ◽  
Laura Domingo Rodriguez ◽  
Vincent Kappes ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Micro Rna ◽  
Projection Neurons ◽  
Cocaine Exposure ◽  
Cell Type ◽  
Mrna Targets ◽  
Cocaine Seeking ◽  
Micro Rnas

The persistent and experience-dependent nature of drug addiction may result in part from epigenetic alterations, including non-coding micro-RNAs (miRNAs), which are both critical for neuronal function and modulated by cocaine in the striatum. Two major striatal cell populations, the striato-nigral and striato-pallidal projection neurons, express respectively the D1 (D1-SPNs) and D2 (D2-SPNs) dopamine receptor, and display distinct but complementary functions in drug-evoked responses. However, a cell-type-specific role for miRNAs action has yet to be clarified. Here, we evaluated the expression of a subset of miRNAs proposed to modulate cocaine effects in the nucleus accumbens (NAc) and dorsal striatum (DS) upon sustained cocaine exposure in mice and showed that these selected miRNAs were preferentially up-regulated in the NAc. We then focused on miR-1 considering the important role of some of its predicted mRNA targets, such as fosb and npas4, in the effects of cocaine. We validated these targets in vitro and in vivo and further showed that overexpression of miR-1 in D1-SPNs of the DS reduced cocaine-induced CPP reinstatement, whereas it increased cue-induced reinstatement of cocaine-SA, without affecting other cocaine-mediated adaptive behavior. In addition, miR-1 overexpression in D2-SPNs of the DS reduced the motivation to self-administer cocaine but did not modify other measured behaviors. Together, our results highlight a precise cell-type- and region-specific control of relapse to cocaine-seeking behaviors by miR-1, and illustrate the importance of cell-specific investigations.

scholarly journals Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction

2019 ◽  
Author(s):  
Opeyemi Alabi ◽  
Mara Robinson ◽  
Michael Fortunato ◽  
Joe W. Kable ◽  
Marc V. Fuccillo
Keyword(s):  
Decision Making ◽  
Normal Function ◽  
Reward Processing ◽  
Projection Neurons ◽  
Choice Data ◽  
Behavioral Alterations ◽  
Gene Ablation ◽  
Reinforcement Learning Models ◽  
Knockout Animals

SUMMARYGoal-directed behaviors, complex action sequences that maximize reward, are essential for normal function and are significantly impaired across neuropsychiatric disorders. Despite extensive associations between genetic mutations and these brain disorders, the mechanisms by which candidate genes contribute to goal-directed dysfunction remains unclear, owing to challenges in (1) describing aspects of reward processing that drive goal-directed dysfunction, (2) localizing these deficits to specific brain circuits and (3) relating changes in physiology to behavioral alterations. Here we examined mice with mutations in Neurexin1α, a presynaptically-localized adhesion molecule with widespread neuropsychiatric dis ease association, in value-based decision-making paradigms. We found that Neurexin1α knockout animals exhibited blunted choice bias towards outcomes associated with greater benefits. Mutant mice were similarly impaired in avoiding costlier, benefit-neutral actions. Analysis of trial-by-trial choice data via reinforcement learning models suggested these behavioral patterns were driven largely by deficits in the updating and representation of choice values. Employing conditional gene ablation and region-specific Cre-recombinase strains, we revealed that Neurexin1α disruption within forebrain excitatory projection neurons, but not thalamic population s, recapitulated most aspects of the whole-brain knockout phenotype. Finally, utilizing in vivo recordings of direct pathway spiny neuron population calcium activity, we demonstrated that selective knockout of Neurexin1α within forebrain excitatory neurons disrupts reward-associated neural signals within striatum, a major site of feedback-based learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in reward-associated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

scholarly journals D1 and D2 systems converge in the striatum to update goal-directed learning

2019 ◽  
Author(s):  
Miriam Matamales ◽  
Alice E. McGovern ◽  
Jia Dai Mi ◽  
Stuart B. Mazzone ◽  
Bernard W. Balleine ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Behavioral Control ◽  
Dorsal Striatum ◽  
Projection Neurons ◽  
Extinction Learning ◽  
Striatal Projection Neurons ◽  
New Learning ◽  
Large Ensembles ◽  
Directed Learning

AbstractExtinction learning allows animals to withhold voluntary actions that are no longer related to reward and so provides a major source of behavioral control. Although such learning is thought to depend on dopamine signals in the striatum, the way the circuits mediating goal-directed control are reorganized during new learning remains unknown. Here, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of striatal projection neurons (SPNs) expressing dopamine receptor type 1 (D1-SPNs) or 2 (D2-SPNs) in mice, we demonstrate an extensive and dynamic D2- to D1-SPN trans-modulation across the dorsal striatum that is necessary for updating previous goal-directed learning. Our findings suggest that D2-SPNs suppress the influence of outdated D1-SPN plasticity within functionally relevant striatal territories to reshape volitional action.

scholarly journals A neural network framework for cognitive bias

2017 ◽  
Author(s):  
J. E. Korteling ◽  
Anne-Marie Brouwer ◽  
Alexander Toet
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Decision Making ◽  
Cognitive Bias ◽  
Cognitive Biases ◽  
Relevant Information ◽  
Theoretical Perspectives ◽  
Human Decision ◽  
Underlying Mechanisms

Human decision making shows systematic simplifications and deviations from the tenets of rationality (‘heuristics’) that may lead to suboptimal decisional outcomes (‘cognitive biases’). There are currently three prevailing theoretical perspectives on the origin of heuristics and cognitive biases: a cognitive-psychological, an ecological and an evolutionary perspective. However, these perspectives are mainly descriptive and none of them provides an overall explanatory framework for the underlying mechanisms of cognitive biases.To enhance our understanding of cognitive heuristics and biases we propose a neural network framework for cognitive biases, which explains why our brain systematically tends to default to heuristic (‘Type 1’) decision making. We argue that many cognitive biases arise from intrinsic brain mechanisms that are fundamental for the working of biological neural networks. In order to substantiate our viewpoint, we discern and explain four basic neural network principles: (1) Association, (2) Compatibility (3) Retainment, and (4) Focus. These principles are inherent to (all) neural networks which were originally optimized to perform concrete biological, perceptual, and motor functions. They form the basis for our inclinations to associate and combine (unrelated) information, to prioritize information that is compatible with our present state (such as knowledge, opinions and expectations), to retain given information that sometimes could better be ignored, and to focus on dominant information while ignoring relevant information that is not directly activated. The supposed mechanisms are complementary and not mutually exclusive. For different cognitive biases they may all contribute in varying degrees to distortion of information. The present viewpoint not only complements the earlier three viewpoints, but also provides a unifying and binding framework for many cognitive bias phenomena.

Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

2020 ◽  
Vol 27 (12) ◽  
pp. 1955-1996 ◽  
Author(s):  
Antonio Speciale ◽  
Antonella Saija ◽  
Romina Bashllari ◽  
Maria Sofia Molonia ◽  
Claudia Muscarà ◽  
...  
Keyword(s):  
Human Health ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Antioxidant Defenses ◽  
Noncommunicable Diseases ◽  
Protective Effects ◽  
Pathological Conditions ◽  
Chronic Pulmonary Diseases ◽  
Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

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