Synapse-specific opioid modulation of thalamo-cortico-striatal circuits

Birdsong, William T.; Jongbloets, Bart C.; Engeln, Kim A; Wang, Dong; Scherrer, Grégory; Mao, Tianyi

doi:10.7554/elife.45146

Cited by 53 publications

(71 citation statements)

References 60 publications

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“…While many others have reported the effects of MORs on glutamatergic synaptic transmission in dorsal striatum 5,25,28,29,31 , until recently, only one other study has specifically explored regulation of DMS transmission via presynaptic MORs 28 . These investigators found that the only source of MOR-mediated depression of glutamatergic transmission in the DMS occurs at thalamic inputs 28 . Our findings contradict this study, but there are a few possible explanations for the different findings.…”

Section: Discussionmentioning

confidence: 99%

Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum

Muñoz

Haggerty

Atwood

2020

Sci Rep

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The dorsal striatum is a brain region involved in action control, with dorsomedial striatum (DMS) mediating goal-directed actions and dorsolateral striatum (DLS) mediating habitual actions. Presynaptic long-term synaptic depression (LTD) plasticity at glutamatergic inputs to dorsal striatum mediates many dorsal striatum-dependent behaviors and disruption of LTD influences action control. Our previous work identified mu opioid receptors (MORs) as mediators of synapse-specific forms of synaptic depression at a number of different DLS synapses. We demonstrated that anterior insular cortex inputs are the sole inputs that express alcohol-sensitive MOR-mediated LTD (mOP-LTD) in DLS. Here, we explore mOP-LTD in DMS using mouse brain slice electrophysiology. We found that contrary to DLS, DMS mOP-LTD is induced by activation of MORs at inputs from both anterior cingulate and medial prefrontal cortices as well as at basolateral amygdala inputs and striatal cholinergic interneuron synapses on to DMS medium spiny neurons, suggesting that MOR synaptic plasticity in DMS is less synapse-specific than in DLS. Furthermore, only mOP-LTD at cortical inputs was sensitive to alcohol's deleterious effects. These results suggest that alcohol-induced neuroadaptations are differentially expressed in a synapse-specific manner and could be playing a role in alterations of goal-directed and habitual behaviors. Alcohol exposure, both acute and chronic, leads to changes in brain function from the genetic level through to changes in cellular function and network alterations 1-4. A common outcome of alcohol-induced cellular adaptations are changes in synaptic plasticity that likely underlie altered neurocircuit function 5,6. One component of alcohol use disorder is a transition from flexible goal-directed alcohol use to more habitual or compulsive use and this is paralleled by a transition in the activity between the dorsomedial (DMS) and the dorsolateral striatum (DLS) subregions of the dorsal striatum 7,8. The dorsal striatum is the input nucleus of the basal ganglia and is a key region involve in goal-directed learning and habit formation, where the DMS has a primary role in the control of outcome-driven behavior and learning and the DLS is important for stimulus-driven behavior and learning 7-12. As alcohol use shifts from being outcome-driven to becoming more stimulus-driven and compulsive in nature during alcohol use disorder development, the balance of action control moves from DMS to DLS 7,8,13. The specialized roles in action control of these two dorsal striatal subregions suggest that the neural circuitry of these two areas are differentially affected by ethanol during the development of alcohol use disorders 14-16. GABAergic medium spiny neurons (MSNs) are the striatal output neurons and comprise 95% of dorsal striatal neurons 17. MSNs receive glutamatergic inputs from cortex, thalamus, basolateral amygdala, and cholinergic interneurons (CINs) 18-20. Despite the similarities in neuronal composition and synapse types, the unique inne...

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Section: Discussionmentioning

confidence: 99%

Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum

Muñoz

Haggerty

Atwood

2020

Sci Rep

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“…δ -Opioid receptors inhibit GABA release from patches of MOR-rich neurons in striatum ( Banghart et al, 2015 ). The activation of MORs in the striatum decreases excitatory afferents from thalamic projections, whereas δ -opioid receptor activation disinhibits neurons in the anterior cingulate cortex to increase excitatory afferent input to the striatum ( Birdsong et al, 2019 ). Thus, the site(s) of receptor activation can have diverse effects on the final output of the medium spiny neurons in the striatum.…”

Section: Cellular Tolerance and Acute Desensitization: Are They Separmentioning

confidence: 99%

“…Selective optical activation of neuron terminals coupled with opioid receptor pharmacology has yielded a greater understanding of opioid-sensitive neural circuits. This approach, in combination with the ability to knock out receptors in various brain areas using conditional MOR knockout mice, has rapidly advanced the understanding of the central actions of opioids in controlling physiologic processes ( Charbogne et al, 2017 ; Birdsong et al, 2019 ). Finally, studies on the role of endogenous opioids in the brain are now approachable with the combination of selective activation of peptide-containing neurons and the developing area of genetically expressed peptide sensors.…”

Section: Introductionmentioning

confidence: 99%

Recent Progress in Opioid Research from an Electrophysiological Perspective

Birdsong¹,

Williams²

2020

Mol Pharmacol

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Electrophysiological approaches provide powerful tools to further our understanding of how different opioids affect signaling through opioid receptors; how opioid receptors modulate circuitry involved in processes such as pain, respiration, addiction, and feeding; and how receptor signaling and circuits are altered by physiologic challenges, such as injury, stress, and chronic opioid treatment. The use of genetic manipulations to alter or remove μ -opioid receptors (MORs) with anatomic and cell type specificity and the ability to activate or inhibit specific circuits through opto- or chemogenetic approaches are being used in combination with electrophysiological, pharmacological, and systems-level physiology experiments to expand our understanding of the beneficial and maladaptive roles of opioids and opioid receptor signaling. New approaches for studying endogenous opioid peptide signaling and release and the dynamics of these systems in response to chronic opioid use, pain, and stress will add another layer to our understanding of the intricacies of opioid modulation of brain circuits. This understanding may lead to new targets or approaches for drug development or treatment regimens that may affect both acute and long-term effects of manipulating the activity of circuits involved in opioid-mediated physiology and behaviors. This review will discuss recent advancements in our understanding of the role of phosphorylation in regulating MOR signaling, as well as our understanding of circuits and signaling pathways mediating physiologic behaviors such as respiratory control, and discuss how electrophysiological tools combined with new technologies have and will continue to advance the field of opioid research. SIGNIFICANCE STATEMENT This review discusses recent advancements in our understanding of μ -opioid receptor (MOR) function and regulation and the role of electrophysiological approaches combined with new technologies in pushing the field of opioid research forward. This covers regulation of MOR at the receptor level, adaptations induced by chronic opioid treatment, sites of action of MOR modulation of specific brain circuits, and the role of the endogenous opioid system in driving physiology and behavior through modulation of these brain circuits.

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“…Presynaptically expressed MORs inhibit glutamatergic excitatory synaptic transmission to SPNs similarly in both striosome and matrix compartments (Miura et al, 2007). While it was initially presumed that this MOR-mediated inhibition occurred at corticostriatal synapses (Blomeley & Bracci, 2011;Miura et al, 2007), more recent studies have shown that thalamostriatal inputs are the targets of MORs, while corticostriatal inputs are attenuated by DORs (Atwood, Kupferschmidt, & Lovinger, 2014;Birdsong et al, 2019). Although opioid receptor-mediated attenuation of excitatory inputs to SPNs may be similar across compartments, attenuation of inhibitory inputs is not.…”

Section: Opioid Receptorsmentioning

confidence: 99%

Compartmental function and modulation of the striatum

Prager

Plotkin

2019

J of Neuroscience Research

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The striatum plays a central role in guiding numerous complex behaviors, ranging from motor control to action selection and reward learning. The diverse responsibilities of the striatum are reflected by the complexity of its organization. In this review, we will summarize what is currently known about the compartmental layout of the striatum, an organizational principle that is crucial for allowing the striatum to guide such a diverse array of behaviors. We will focus on the anatomical and functional properties of striosome (patch) and matrix compartments of the striatum, and how the engagement of these compartments is uniquely controlled by their afferents, intrinsic properties, and neuromodulation. We will give examples of how advances in technology have opened the door to functionally dissecting the striatum's compartmental design, and close by offering thoughts on the future and relevance for human disease.

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Synapse-specific opioid modulation of thalamo-cortico-striatal circuits

Cited by 53 publications

References 60 publications

Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum

Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum

Recent Progress in Opioid Research from an Electrophysiological Perspective

Compartmental function and modulation of the striatum

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