Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum

Atwood, Brady K.; Kupferschmidt, David A.; Lovinger, David M.

doi:10.1038/nn.3652

Cited by 111 publications

(205 citation statements)

References 46 publications

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“…It is well established that MOR and DOR agonists suppress excitatory transmission onto SPNs by 10–30% in both patches and matrix (Atwood et al, 2014; Blomeley and Bracci, 2011; Jiang and North, 1992; Miura et al, 2007). We therefore focused on inhibitory synaptic transmission.…”

Section: Resultsmentioning

confidence: 99%

“…Because opioids have been reported to reduce glutamate release in both patches and matrix (Atwood et al, 2014; Jiang and North, 1992; Miura et al, 2007), suppression of excitation might counteract suppression of inhibition and prevent the predicted facilitation of spiking in patches by enk. Therefore, we measured the consequence of enk application on action potential firing induced by cortico-striatal activation.…”

Section: Resultsmentioning

confidence: 99%

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Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors

Banghart

Neufeld

Wong

et al. 2015

Neuron

103

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SUMMARY Opioid neuropeptides and their receptors are evolutionarily conserved neuromodulatory systems that profoundly influence behavior. In dorsal striatum, which expresses the endogenous opioid enkephalin, patches (or striosomes) are limbic-associated subcompartments enriched in mu opioid receptors. The functional implications of opioid signaling in dorsal striatum and the circuit elements in patches regulated by enkephalin are unclear. Here, we examined how patch output is modulated by enkephalin and identified the underlying circuit mechanisms. We found that patches are relatively devoid of parvalbumin-expressing interneurons and exist as self-contained inhibitory microcircuits. Enkephalin suppresses inhibition onto striatal projection neurons selectively in patches, thereby disinhibiting their firing in response to cortical input. The majority of this neuromodulation is mediated by delta, not mu opioid receptors, acting specifically on intra-striatal collateral axons of striatopallidal neurons. These results suggest that enkephalin gates limbic information flow in dorsal striatum, acting via a patch-specific function for delta opioid receptors.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors

Banghart

Neufeld

Wong

et al. 2015

Neuron

103

View full text Add to dashboard Cite

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“…Given the known interactions between EtOH and the opioid system (Volpicelli et al, 1992;Drews and Zimmer, 2010), and that activation of these G i/o -coupled opioid receptors is capable of inducing striatal presynaptic LTD (Atwood et al, 2014a), we next assessed whether EtOH-LTD occurs in an opioid receptor-dependent fashion. MSN-MSN EtOH-LTD was not eliminated in the presence of naloxone, a pan opioid receptor antagonist (oIPSC amplitude = 80.03 ± 6.94% of baseline, t = 2.88, df = 6, p = 0.03, Figure 3a).…”

Section: Fsi-msn Etoh-ltd Is Dor Dependentmentioning

confidence: 99%

Ethanol Disinhibits Dorsolateral Striatal Medium Spiny Neurons Through Activation of A Presynaptic Delta Opioid Receptor

Patton

Roberts

Lovinger

et al. 2015

Neuropsychopharmacol

Self Cite

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The dorsolateral striatum mediates habit formation, which is expedited by exposure to alcohol. Across species, alcohol exposure disinhibits the DLS by dampening GABAergic transmission onto this structure's principal medium spiny projection neurons (MSNs), providing a potential mechanistic basis for habitual alcohol drinking. However, the molecular and circuit components underlying this disinhibition remain unknown. To examine this, we used a combination of whole-cell patch-clamp recordings and optogenetics to demonstrate that ethanol potently depresses both MSN-and fast-spiking interneuron (FSI)-MSN GABAergic synaptic transmission in the DLS. Concentrating on the powerfully inhibitory FSI-MSN synapse, we further show that acute exposure of ethanol (50 mM) to striatal slices activates delta opioid receptors that reside on FSI axon terminals and negatively couple to adenylyl cyclase to induce a long-term depression of GABA release onto both direct and indirect pathway MSNs. These findings elucidate a mechanism through which ethanol may globally disinhibit the DLS.

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“…Striatal CB1Rs may thus be crucial for establishing behavioral patterns that are directed compulsively toward drug usage (Gerdeman et al 2003). Interestingly, studies from several laboratories have demonstrated disruption of striatal eCB-LTD following acute and protracted exposure to drugs of abuse (Fourgeaud et al 2004;Clarke & Adermark 2010;Adermark et al 2011;Atwood, Kupferschmidt, & Lovinger 2014). Therapeutic approaches aimed at restoring eCB-mediated synaptic plasticity might thus potentially have impact on the treatment of addiction (Zlebnik & Cheer 2016).…”

Section: Introductionmentioning

confidence: 99%

Acute and chronic modulation of striatal endocannabinoid‐mediated plasticity by nicotine

et al. 2018

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The endocannabinoid (eCB) system modulates several phenomena related to addictive behaviors, and drug-induced changes in eCB signaling have been postulated to be important mediators of physiological and pathological rewardrelated synaptic plasticity. Here, we studied eCB-mediated long-term depression (eCB-LTD) in the dorsolateral striatum, a brain region critical for acquisition of habitual and automatic behavior. We report that nicotine differentially affects ex vivo eCB signaling depending on previous exposure in vivo. In the nicotine-naïve brain, nicotine facilitates eCB-signaling and LTD, whereas tolerance develops to this facilitating effect after subchronic exposure in vivo. In the end, a progressive impairment of eCB-induced LTD is established after protracted withdrawal from nicotine. Endocannabinoid-LTD is reinstated 6 months after the last drug injection, but a brief period of nicotine re-exposure is sufficient to yet again impair eCB-signaling. LTD induced by the cannabinoid 1 receptor agonist WIN55,212-2 is not affected, suggesting that nicotine modulates eCB production or release. Nicotine-induced facilitation of eCB-LTD is occluded by the dopamine D2 receptor agonist quinpirole, and by the muscarinic acetylcholine receptor antagonist scopolamine. In addition, the same compounds restore eCB-LTD during protracted withdrawal. Nicotine may thus modulate eCB-signaling by affecting dopaminergic and cholinergic neurotransmission in a long-lasting manner. Overall, the data presented here suggest that nicotine facilitates eCB-LTD in the initial phase, which putatively could promote neurophysiological and behavioral adaptations to the drug. Protracted withdrawal, however, impairs eCB-LTD, which may influence or affect the ability to maintain cessation.

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Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum

Cited by 111 publications

References 46 publications

Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors

Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors

Ethanol Disinhibits Dorsolateral Striatal Medium Spiny Neurons Through Activation of A Presynaptic Delta Opioid Receptor

Acute and chronic modulation of striatal endocannabinoid‐mediated plasticity by nicotine

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