Browsing by Author "Yin, Yuexi"

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    Converging Effects of Chronic Pain and Binge Alcohol Consumption on Anterior Insular Cortex Neurons Projecting to the Dorsolateral Striatum in Male Mice
    (Society for Neuroscience, 2024-04-17) Yin, Yuexi; Haggerty, David L.; Zhou, Shudi; Atwood, Brady K.; Sheets, Patrick L.; Pharmacology and Toxicology, School of Medicine
    Chronic pain and alcohol use disorder (AUD) are highly comorbid, and patients with chronic pain are more likely to meet the criteria for AUD. Evidence suggests that both conditions alter similar brain pathways, yet this relationship remains poorly understood. Prior work shows that the anterior insular cortex (AIC) is involved in both chronic pain and AUD. However, circuit-specific changes elicited by the combination of pain and alcohol use remain understudied. The goal of this work was to elucidate the converging effects of binge alcohol consumption and chronic pain on AIC neurons that send projections to the dorsolateral striatum (DLS). Here, we used the Drinking-in-the-Dark (DID) paradigm to model binge-like alcohol drinking in mice that underwent spared nerve injury (SNI), after which whole-cell patch-clamp electrophysiological recordings were performed in acute brain slices to measure intrinsic and synaptic properties of AIC→DLS neurons. In male, but not female, mice, we found that SNI mice with no prior alcohol exposure consumed less alcohol compared with sham mice. Electrophysiological analyses showed that AIC→DLS neurons from SNI-alcohol male mice displayed increased neuronal excitability and increased frequency of miniature excitatory postsynaptic currents. However, mice exposed to alcohol prior to SNI consumed similar amounts of alcohol compared with sham mice following SNI. Together, our data suggest that the interaction of chronic pain and alcohol drinking have a direct effect on both intrinsic excitability and synaptic transmission onto AIC→DLS neurons in mice, which may be critical in understanding how chronic pain alters motivated behaviors associated with alcohol.
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    Converging Effects of Chronic Pain and Binge Alcohol Consumption on Corticostriatal Neurons and the Effects of Acute Alcohol Exposure on the Medial Prefrontal Cortex
    (2024-07) Yin, Yuexi; Atwood, Brady K.; Baucum, AJ; Hopf, Woody; McKinzie, David L.; Sheets, Patrick L.
    Chronic pain and alcohol use disorder (AUD) are highly comorbid, but whether the two conditions share common brain pathways is unclear. Prior work shows that the anterior insular cortex (AIC) is involved in both chronic pain and alcohol use disorder. However, circuit-specific changes elicited by the combination of pain and alcohol use remain understudied. The goal of this work was to elucidate the converging effects of binge alcohol consumption and chronic pain on AIC neurons that send projections to the dorsolateral striatum (DLS). Here, we used the Drinking-in-the-Dark paradigm to model binge-like alcohol drinking in mice that underwent spared nerve injury (SNI). We found that SNI male mice with no prior alcohol exposure consumed less alcohol compared to sham mice. Electrophysiological analyses showed that AIC-DLS neurons from SNI-alcohol male mice displayed increased neuronal excitability and increased frequency of miniature excitatory postsynaptic currents. However, mice exposed to alcohol prior to SNI consumed similar amounts of alcohol compared to sham mice following SNI. Together, our data suggest that the pain and alcohol interaction can sensitize the AIC-DLS circuit in mice, which may be critical in understanding how chronic pain alters motivated behaviors associated with alcohol. My second goal was to assess the acute pharmacological effects of alcohol on prodynorphin-expressing neurons in the prelimbic cortex (PLPdyn+), a subregion of the medial prefrontal cortex (mPFC). Kappa opioid receptor (KOR) system dysregulation contributes to alcohol addiction. Prodynorphin (Pdyn) is the precursor peptide to the endogenous opioid ligand for KORs. Early studies demonstrated that acute alcohol exposure elevates Pdyn mRNA expression in the mPFC. However, its functional effects on Pdyn-expressing neurons are not known. Here, we used whole-cell patch-clamp electrophysiology in acute brain slices and glutamate-uncaging via laser scanning photo to map local excitatory and inhibitory inputs onto PL neurons. We found that acute alcohol increases local inhibitory inputs to both layer 2/3 PLPdyn+ and PLPdyn- neurons but has no effect on excitatory inputs. Under untreated conditions, PLPdyn+ neurons show stronger local excitatory inputs compared to PLPdyn- neurons. Overall, these data suggest that acute alcohol intoxication inhibits intracortical circuit of PL neurons regardless of neuronal subtypes.
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    Mouse models of surgical and neuropathic pain produce distinct functional alterations to prodynorphin expressing neurons in the prelimbic cortex
    (Elsevier, 2023-02-13) Zhou, Shudi; Yin, Yuexi; Sheets, Patrick L.; Pharmacology and Toxicology, School of Medicine
    The medial prefrontal cortex (mPFC) consists of a heterogeneous population of neurons that respond to painful stimuli, and our understanding of how different pain models alter these specific mPFC cell types remains incomplete. A distinct subpopulation of mPFC neurons express prodynorphin (Pdyn+), the endogenous peptide agonist for kappa opioid receptors (KORs). Here, we used whole cell patch clamp for studying excitability changes to Pdyn expressing neurons in the prelimbic region of the mPFC (PLPdyn+ neurons) in mouse models of surgical and neuropathic pain. Our recordings revealed that PLPdyn+ neurons consist of both pyramidal and inhibitory cell types. We find that the plantar incision model (PIM) of surgical pain increases intrinsic excitability only in pyramidal PLPdyn+ neurons one day after incision. Following recovery from incision, excitability of pyramidal PLPdyn+ neurons did not differ between male PIM and sham mice, but was decreased in PIM female mice. Moreover, the excitability of inhibitory PLPdyn+ neurons was increased in male PIM mice, but was with no difference between female sham and PIM mice. In the spared nerve injury model (SNI), pyramidal PLPdyn+ neurons were hyperexcitable at both 3 days and 14 days after SNI. However, inhibitory PLPdyn+ neurons were hypoexcitable at 3 days but hyperexcitable at 14 days after SNI. Our findings suggest different subtypes of PLPdyn+ neurons manifest distinct alterations in the development of different pain modalities and are regulated by surgical pain in a sex-specific manner. Our study provides information on a specific neuronal population that is affected by surgical and neuropathic pain.