scholarly journals Dopaminergic Regulation of Striatal Interneurons in Reward and Addiction: Focus on Alcohol

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Rhona Clarke ◽  
Louise Adermark
Keyword(s):  
Physiological Activity ◽  
Dorsal Striatum ◽  
Primary Component ◽  
Medium Spiny Neurons ◽  
Dopaminergic Transmission ◽  
Cholinergic Interneurons ◽  
Guided Learning ◽  
Striatal Interneurons ◽  
Dopaminergic Regulation

Corticobasal ganglia networks coursing through the striatum are key structures for reward-guided behaviors. The ventral striatum (nucleus accumbens (nAc)) and its reciprocal connection with the ventral tegmental area (VTA) represent a primary component of the reward system, but reward-guided learning also involves the dorsal striatum and dopaminergic inputs from the substantia nigra. The majority of neurons in the striatum (>90%) are GABAergic medium spiny neurons (MSNs), but both the input to and the output from these neurons are dynamically controlled by striatal interneurons. Dopamine is a key neurotransmitter in reward and reward-guided learning, and the physiological activity of GABAergic and cholinergic interneurons is regulated by dopaminergic transmission in a complex manner. Here we review the role of striatal interneurons in modulating striatal output during drug reward, with special emphasis on alcohol.

scholarly journals Orbitofrontal and Thalamic Influences on Striatal Involvement in Human Reversal Learning

2018 ◽  
Author(s):  
Tiffany Bell ◽  
Angela Langdon ◽  
Michael Lindner ◽  
William Lloyd ◽  
Anastasia Christakou
Keyword(s):  
Reversal Learning ◽  
Animal Studies ◽  
Dorsal Striatum ◽  
Response Strategy ◽  
Cholinergic Interneurons ◽  
Learning Tasks ◽  
Initial Learning ◽  
Before And After ◽  
Psychophysiological Interaction

ABSTRACTCognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that connectivity between the striatum and both the lateral orbitofrontal cortex (lOFC) and CM-Pf pathways increased during reversal, but not initial learning. However, while the strength of lOFC-striatal connectivity was associated with the speed of the reversal, the strength of CM-Pf-striatal connectivity was associated specifically with the quality of the reversal (reduced regressive errors). These findings expand our understanding of flexibility mechanisms in the human brain, bridging the gap with animal studies of this system.

scholarly journals The Role of Mesostriatal Dopamine System and Corticostriatal Glutamatergic Transmission in Chronic Pain

2021 ◽  
Vol 11 (10) ◽  
pp. 1311
Author(s):  
Barbara Ziółkowska
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
Persistent Pain ◽  
Pain Modulation ◽  
Medium Spiny Neurons ◽  
Analgesic Effects

There is increasing recognition of the involvement of the nigrostriatal and mesolimbic dopamine systems in the modulation of chronic pain. The first part of the present article reviews the evidence indicating that dopamine exerts analgesic effects during persistent pain by stimulating the D2 receptors in the dorsal striatum and nucleus accumbens (NAc). Thereby, dopamine inhibits striatal output via the D2 receptor-expressing medium spiny neurons (D2-MSN). Dopaminergic neurotransmission in the mesostriatal pathways is hampered in chronic pain states and this alteration maintains and exacerbates pain. The second part of this article focuses on the glutamatergic inputs from the medial prefrontal cortex to the NAc, their activity changes in chronic pain, and their role in pain modulation. Finally, interactions between dopaminergic and glutamatergic inputs to the D2-MSN are considered in the context of persistent pain. Studies using novel techniques indicate that pain is regulated oppositely by two independent dopaminergic circuits linking separate parts of the ventral tegmental area and of the NAc, which also interact with distinct regions of the medial prefrontal cortex.

scholarly journals What Is the Role of Thalamostriatal Circuits in Learning Vocal Sequences?

2021 ◽  
Vol 15 ◽  
Author(s):  
Lei Xiao ◽  
Todd F. Roberts
Keyword(s):  
Reinforcement Learning ◽  
Song Learning ◽  
Medium Spiny Neurons ◽  
Cholinergic Interneurons ◽  
Related Information ◽  
Spiny Neurons ◽  
Motor Information ◽  
Area X ◽  
Reinforcement Learning Model

Basal ganglia (BG) circuits integrate sensory and motor-related information from the cortex, thalamus, and midbrain to guide learning and production of motor sequences. Birdsong, like speech, is comprised of precisely sequenced vocal elements. Learning song sequences during development relies on Area X, a vocalization related region in the medial striatum of the songbird BG. Area X receives inputs from cortical-like pallial song circuits and midbrain dopaminergic circuits and sends projections to the thalamus. It has recently been shown that thalamic circuits also send substantial projections back to Area X. Here, we outline a gated-reinforcement learning model for how Area X may use signals conveyed by thalamostriatal inputs to direct song learning. Integrating conceptual advances from recent mammalian and songbird literature, we hypothesize that thalamostriatal pathways convey signals linked to song syllable onsets and offsets and influence striatal circuit plasticity via regulation of cholinergic interneurons (ChIs). We suggest that syllable sequence associated vocal-motor information from the thalamus drive precisely timed pauses in ChIs activity in Area X. When integrated with concurrent corticostriatal and dopaminergic input, this circuit helps regulate plasticity on medium spiny neurons (MSNs) and the learning of syllable sequences. We discuss new approaches that can be applied to test core ideas of this model and how associated insights may provide a framework for understanding the function of BG circuits in learning motor sequences.

scholarly journals Accumbens cholinergic interneurons mediate cue-induced nicotine seeking and associated glutamatergic plasticity

2020 ◽  
Author(s):  
Jonna M. Leyrer-Jackson ◽  
Michael Holter ◽  
Paula F. Overby ◽  
Jason M. Newbern ◽  
Michael D. Scofield ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Release ◽  
Neuronal Population ◽  
Medium Spiny Neurons ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Cholinergic Interneurons ◽  
Seeking Behavior ◽  
Underlying Mechanisms

AbstractNicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs) which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes in unknown. ChIs represent less than 1% of the accumbens neuronal population yet are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine seeking behavior. Using chemogenetics transgenic rats that express Cre under the control of the choline acetyltransferase (ChAT) promoter, ChIs were bi-directionally manipulated prior to cue-induced reinstatement. Following nicotine self-administration and extinction training, ChIs were activated or inhibited prior to a cue reinstatement session. Following reinstatement, whole-cell electrophysiology from NAcore MSNs was used to assess changes in plasticity, measured via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) / N-Methyl-D-Aspartate (NMDA) (A/N) ratios. Chemogenetic inhibition of ChIs inhibited cued nicotine seeking and resulted in decreased A/N, whereas activation of ChIs had no effect, demonstrating that ChI inhibition prevents transient synaptic potentiation (t-SP) associated with cue-induced nicotine seeking. To assess potential underlying mechanisms, accumbens α4β2- and α7-containing nicotinic ACh receptors (nAChRs) were pharmacologically inhibited and MSN synaptic morphology was assessed following reinstatement. Inhibition of both nAChR subtypes prevented cue-induced nicotine seeking and t-SP (measured via changes in spine head diameter). Together, these results demonstrate that these neurons mediate cue-induced nicotine reinstatement and underlying synaptic plasticity within the NAcore.

scholarly journals Selective Role of RGS9-2 in Regulating Retrograde Synaptic Signaling of Indirect Pathway Medium Spiny Neurons in Dorsal Striatum

2018 ◽  
Vol 38 (32) ◽  
pp. 7120-7131 ◽  
Author(s):  
Chenghui Song ◽  
Garret R. Anderson ◽  
Laurie P. Sutton ◽  
Maria Dao ◽  
Kirill A. Martemyanov
Keyword(s):  
Dorsal Striatum ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Synaptic Signaling ◽  
Spiny Neurons

STEROID HORMONE METABOLISM IN RESPONSIVE TISSUES IN VITRO

1971 ◽  
Vol 68 (1_Suppl) ◽  
pp. S279-S294 ◽  
Author(s):  
Paul Robel
Keyword(s):  
Steroid Hormone ◽  
Physiological Activity ◽  
Physiological State ◽  
Target Cells ◽  
Target Tissue ◽  
Hormone Metabolism ◽  
Metabolizing Enzymes ◽  
Relationship Of

ABSTRACT Of the information available on steroid hormone metabolism in responsive tissues, only that relating hormone metabolism to physiological activity is reviewed, i. e. metabolite activity in isolated in vitro systems, binding of metabolites to target tissue receptors, specific steroid hormone metabolizing enzymes and relationship of hormone metabolism to target organ physiological state. Further, evidence is presented in the androgen field, demonstrating 5α-reduced metabolites, formed inside the target cells, as active compounds. This has led to a consideration of testosterone as a »prehormone«. The possibility that similar events take place in tissues responding to progesterone is discussed. Finally, the role of hormone metabolism in the regulation of hormone availability and/or renewal in target cells is discussed. In this context, reference is made to the potential role of plasma binding proteins and cytosol receptors.

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