scholarly journals Error-related Signaling in Nucleus Accumbens D2 Receptor-expressing Neurons Guides Avoidance-based Goal-directed Behavior

2022 ◽  
Author(s):  
Tadaaki Nishioka ◽  
Tom Macpherson ◽  
Kosuke Hamaguchi ◽  
Takatoshi Hikida
Keyword(s):  
Nucleus Accumbens ◽  
Behavioral Control ◽  
D2 Receptor ◽  
Environmental Cues ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Cell Type Specific ◽  
Goal Directed Behavior

Abstract Learnt associations between environmental cues and the outcomes they predict (cue-outcome associations) play a major role in behavioral control, guiding not only which responses we should perform, but also which we should avoid, in order to achieve a specific goal. The encoding of such cue-outcome associations, as well as the performance of cue-guided goal-directed behavior, is thought to involve dopamine D1 and D2 receptor-expressing medium spiny neurons (D1-/D2-MSNs) of the nucleus accumbens (NAc). Here, using a visual discrimination task in mice, we assessed the role of NAc D1-/D2-MSNs in cue-guided goal-directed avoidance of inappropriate responding. Cell-type specific neuronal silencing and in-vivo imaging revealed NAc D2-MSNs to selectively contribute to cue-guided avoidance behavior, with activation of NAc D2-MSNs following response error playing an important role in optimizing future goal-directed behavior. Our findings indicate that error-signaling by NAc D2-MSNs underlies the ability to use environmental cues to avoid inappropriate behavior.

scholarly journals Biology and Bias in Cell Type-Specific RNAseq of Nucleus Accumbens Medium Spiny Neurons

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hope Kronman ◽  
Felix Richter ◽  
Benoit Labonté ◽  
Ramesh Chandra ◽  
Shan Zhao ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Medium Spiny Neurons ◽  
Cell Type ◽  
Spiny Neurons ◽  
Cell Type Specific

scholarly journals Binge Alcohol Drinking Alters Synaptic Processing of Executive and Emotional Information in Core Nucleus Accumbens Medium Spiny Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Jenya Kolpakova ◽  
Vincent van der Vinne ◽  
Pablo Giménez-Gómez ◽  
Timmy Le ◽  
In-Jee You ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Alcohol Drinking ◽  
Drugs Of Abuse ◽  
Alcohol Exposure ◽  
Medium Spiny Neurons ◽  
Dependent Manner ◽  
Emotional Information ◽  
Core Nucleus ◽  
Spiny Neurons

The nucleus accumbens (NAc) is a forebrain region mediating the positive-reinforcing properties of drugs of abuse, including alcohol. It receives glutamatergic projections from multiple forebrain and limbic regions such as the prefrontal cortex (PFCx) and basolateral amygdala (BLA), respectively. However, it is unknown how NAc medium spiny neurons (MSNs) integrate PFCx and BLA inputs, and how this integration is affected by alcohol exposure. Because progress has been hampered by the inability to independently stimulate different pathways, we implemented a dual wavelength optogenetic approach to selectively and independently stimulate PFCx and BLA NAc inputs within the same brain slice. This approach functionally demonstrates that PFCx and BLA inputs synapse onto the same MSNs where they reciprocally inhibit each other pre-synaptically in a strict time-dependent manner. In alcohol-naïve mice, this temporal gating of BLA-inputs by PFCx afferents is stronger than the reverse, revealing that MSNs prioritize high-order executive processes information from the PFCx. Importantly, binge alcohol drinking alters this reciprocal inhibition by unilaterally strengthening BLA inhibition of PFCx inputs. In line with this observation, we demonstrate that in vivo optogenetic stimulation of the BLA, but not PFCx, blocks binge alcohol drinking escalation in mice. Overall, our results identify NAc MSNs as a key integrator of executive and emotional information and show that this integration is dysregulated during binge alcohol drinking.

scholarly journals Neuronal signature of an antipsychotic response

2020 ◽  
Author(s):  
Jeffrey Parrilla-Carrero ◽  
Anna Kruyer ◽  
Reda M. Chalhoub ◽  
Courtney Powell ◽  
Shanna Resendez ◽  
...  
Keyword(s):  
D2 Receptor ◽  
Symptom Improvement ◽  
Medium Spiny Neurons ◽  
Principal Mechanism ◽  
Spiny Neurons ◽  
Nmda Channel ◽  
Resolution Imaging ◽  
The Impact ◽  
The Brain

Abstract D2 receptor blockade has been cited as a principal mechanism of action of all antipsychotic medications, but is poorly predictive of symptom improvement or neurophysiological responses recorded using human brain imaging. A potential hurdle in interpreting such human imaging studies arises from the inability to distinguish activity within neuronal subcircuits. We used single cell resolution imaging to record activity in distinct populations of medium spiny neurons in vivo within the mouse ventral striatum, a structure associated with schizophrenia symptoms and antipsychotic therapeutic efficacy. While we expected the antipsychotic haloperidol to excite D2 receptor expressing neurons, we report a strong cellular depression mediated by the hypofunctional NMDA channel, which may be mediated in part by the action of haloperidol on the sigma1 receptor. Altogether, the impact of haloperidol on Ca2+ events in D2 receptor expressing neurons predicted psychomotor inhibition. Our results elucidate mechanisms by which antipsychotics act rapidly in the brain to impact psychomotor outputs.

scholarly journals Cocaine place conditioning strengthens location-specific hippocampal inputs to the nucleus accumbens

2017 ◽  
Author(s):  
Lucas Sjulson ◽  
Adrien Peyrache ◽  
Andrea Cumpelik ◽  
Daniela Cassataro ◽  
György Buzsáki
Keyword(s):  
Nucleus Accumbens ◽  
Drug Exposure ◽  
Physiological Mechanism ◽  
Underlying Mechanism ◽  
Place Conditioning ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Freely Moving ◽  
Dual Site

Conditioned place preference (CPP) is a widely used model of addiction-related behavior whose underlying mechanism is not understood. In this study, we used dual site silicon probe recordings in freely moving mice to examine interactions between the hippocampus and nucleus accumbens in cocaine CPP. We found that CPP was associated with recruitment of nucleus accumbens medium spiny neurons to fire in the cocaine-paired location, and this recruitment was driven predominantly by selective strengthening of hippocampal inputs arising from place cells that encode the cocaine-paired location. These findings provide in vivo evidence that the synaptic potentiation in the accumbens caused by repeated cocaine administration preferentially affects inputs that were active at the time of drug exposure. This provides a potential physiological mechanism by which drug use becomes associated with specific environmental contexts.

scholarly journals Distinct role of nucleus accumbens D2-MSN projections to ventral pallidum in different phases of motivated behavior

2020 ◽  
Author(s):  
Carina Soares-Cunha ◽  
Raquel Correia ◽  
Ana Verónica Domingues ◽  
Bárbara Coimbra ◽  
Nivaldo AP de Vasconcelos ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Behavioral Effect ◽  
Ventral Pallidum ◽  
Medium Spiny Neurons ◽  
Motivated Behavior ◽  
Spiny Neurons ◽  
Reward Delivery ◽  
Instrumental Task ◽  
Motivated Behaviors

AbstractThe nucleus accumbens (NAc) is a key region in motivated behaviors. NAc medium spiny neurons (MSNs) are divided into those expressing dopamine receptor D1 or D2. Classically, D1- and D2-MSNs have been described as having opposing roles in reinforcement but recent evidence suggests a more complex role for D2-MSNs.Here we show that optogenetic modulation of D2-MSN to ventral pallidum (VP) projections during different stages of motivated behavior has contrasting effects in motivation. Activation of D2-MSN-VP projections during a reward-predicting cue results in increased motivational drive, whereas activation at reward delivery results in decreased motivation; optical inhibition has the opposite behavioral effect. In addition, in a free choice instrumental task, animals prefer the lever that originates one pellet in opposition to pellet plus D2-MSN-VP optogenetic activation, and vice versa for optogenetic inhibition.In summary, D2-MSN-VP projections play different (and even opposing) roles in distinct phases of motivated behavior.

scholarly journals Selective modulation of GABAergic tonic current by dopamine in the nucleus accumbens of alcohol-dependent rats

2014 ◽  
Vol 112 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Jing Liang ◽  
Vincent N. Marty ◽  
Yatendra Mulpuri ◽  
Richard W. Olsen ◽  
Igor Spigelman
Keyword(s):  
Nucleus Accumbens ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Medium Spiny Neurons ◽  
Chronic Intermittent Ethanol ◽  
Acid Type ◽  
Tonic Current ◽  
Kinetics Of

The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Alterations in glutamatergic and GABAergic signaling were recently demonstrated in the NAcc of rats after chronic intermittent ethanol (CIE) treatment, a model of alcohol dependence. Here we studied dopamine (DA) modulation of GABAergic signaling and how this modulation might be altered by CIE treatment. We show that the tonic current ( Itonic) mediated by extrasynaptic γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc core is differentially modulated by DA at concentrations in the range of those measured in vivo (0.01–1 μM), without affecting the postsynaptic kinetics of miniature inhibitory postsynaptic currents (mIPSCs). Use of selective D1 receptor (D1R) and D2 receptor (D2R) ligands revealed that Itonic potentiation by DA (10 nM) is mediated by D1Rs while Itonic depression by DA (0.03–1 μM) is mediated by D2Rs in the same MSNs. Addition of guanosine 5′- O-(2-thiodiphosphate) (GDPβS) to the recording pipettes eliminated Itonic decrease by the selective D2R agonist quinpirole (5 nM), leaving intact the quinpirole effect on mIPSC frequency. Recordings from CIE and vehicle control (CIV) MSNs during application of D1R agonist (SKF 38393, 100 nM) or D2R agonist (quinpirole, 2 nM) revealed that SKF 38393 potentiated Itonic to the same extent, while quinpirole reduced Itonic to a similar extent, in both groups of rats. Our data suggest that the selective modulatory effects of DA on Itonic are unaltered by CIE treatment and withdrawal.

scholarly journals Morphology of Human Nucleus Accumbens Neurons Based on the Immunohistochemical Expression of Gad67

2016 ◽  
Vol 17 (4) ◽  
pp. 297-302
Author(s):  
Maja Sazdanovic ◽  
Slobodanka Mitrovic ◽  
Milos Todorovic ◽  
Maja Vulovic ◽  
Dejan Jeremic ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Pyramidal Neurons ◽  
Immunohistochemical Analysis ◽  
Medium Spiny Neurons ◽  
Immunohistochemical Expression ◽  
Spiny Neurons ◽  
Different Types ◽  
Human Brains

Abstract The nucleus accumbens is a part of the ventral striatum along with the caudate nucleus and putamen. The role of the human nucleus accumbens in drug addiction and other psychiatric disorders is of great importance. The aim of this study was to characterize medium spiny neurons in the nucleus accumbens according to the immunohistochemical expression of GAD67. This study was conducted on twenty human brains of both sexes between the ages of 20 and 75. The expression of GAD67 was assessed immunohistochemically, and the characterization of the neurons was based on the shape and size of the soma and the number of impregnated primary dendrites. We showed that neurons of the human nucleus accumbens expressed GAD67 in the neuron soma and in the primary dendrites. An analysis of the cell body morphology revealed the following four different types of neurons: fusiform neurons, fusiform neurons with lateral dendrites, pyramidal neurons and multipolar neurons. An immunohistochemical analysis showed a strong GAD67 expression in GABAergic medium spiny neurons, which could be classifi ed into four different types, and these neurons morphologically correlated with those described by the Golgi study.

scholarly journals Morphine differentially alters the synaptic and intrinsic properties of D1R- and D2R-expressing medium spiny neurons in the nucleus accumbens

2019 ◽  
Author(s):  
Dillon S. McDevitt ◽  
Benjamin Jonik ◽  
Nicholas M. Graziane
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Nucleus Accumbens Shell ◽  
Membrane Excitability ◽  
Action Potential Firing ◽  
Spiny Neurons ◽  
Functional Output

AbstractExposure to opioids reshapes future reward and motivated behaviors partially by altering the functional output of medium spiny neurons (MSNs) in the nucleus accumbens shell. Here, we investigated how morphine, a highly addictive opioid, alters synaptic transmission and intrinsic excitability on dopamine D1-receptor (D1R) expressing and dopamine D2-receptor (D2R) expressing MSNs, the two main output neurons in the nucleus accumbens shell. Using whole-cell electrophysiology recordings, we show, that 24 h abstinence following repeated non-contingent administration of morphine (10 mg/kg, i.p.) in mice reduces miniature excitatory postsynaptic current (mEPSC) frequency and miniature inhibitory postsynaptic current (mIPSC) frequency on D2R-MSNs, with concomitant increases in D2R-MSN intrinsic membrane excitability. We did not observe any changes on synaptic or intrinsic changes on D1R-MSNs. Lastly, in an attempt to determine the integrated effect of the synaptic and intrinsic alterations on the overall functional output of D2R-MSNs, we measured the input-output efficacy by measuring synaptically-driven action potential firing. We found that both D1R-MSN and D2R-MSN output was unchanged following morphine treatment.

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