An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking
Abstract Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associa...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-81390-2 |
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| author | Anders J. Asp Suelen Lucio Boschen Su-Youne Chang Jiwon Kim Jodi L. Silvernail J. Luis Lujan |
| author_facet | Anders J. Asp Suelen Lucio Boschen Su-Youne Chang Jiwon Kim Jodi L. Silvernail J. Luis Lujan |
| author_sort | Anders J. Asp |
| collection | DOAJ |
| description | Abstract Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associated cost of approximately $249 billion annually in the U.S. alone. The effects of alcohol consumption are expected to increase significantly during the COVID-19 pandemic, with alcohol sales increasing by approximately 54%, potentially exacerbating health concerns and risk-taking behaviors. Unfortunately, existing pharmacological and behavioral therapies for AUD are associated with poor success rates, with approximately 40% of individuals relapsing within three years of treatment. Pre-clinical studies have shown that chronic alcohol consumption leads to significant changes in synaptic function within the dorsal medial striatum (DMS), one of the brain regions associated with AUD and responsible for mediating goal-directed behavior. Specifically, chronic alcohol consumption has been associated with hyperactivity of dopamine receptor 1 (D1) medium spiny neurons (MSN) and hypoactivity of dopamine receptor 2 (D1) MSNs within the DMS. Optogenetic, chemogenetic, and transgenic approaches have demonstrated that reducing the D1/D2 MSN signaling imbalance decreases alcohol self-administration in rodent models of AUD. Here, we present an electrical stimulation approach that uses ultra-low (≤ 1 Hz) frequency (ULF) spike-timing-dependent plasticity (STDP) in mouse models of AUD to reduce DMS D1/D2 MSN signaling imbalances by stimulating D1-MSN afferents into the GPi and ACC glutamatergic projections to the DMS in a time-locked stimulation sequence. Our data suggest that GPi/ACC ULF-STDP selectively decreases DMS D1-MSN hyperactivity leading to reduced alcohol consumption without evoking undesired affective behaviors using electrical stimulation rather than approaches requiring genetic modification. This work represents a step towards fulfilling the unmet need for a reliable method of treating severe AUD through cell-type-specific control with clinically available neuromodulation tools. |
| format | Article |
| id | doaj-art-4f571bec079b42d28c11a8fd22369f7b |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4f571bec079b42d28c11a8fd22369f7b2025-08-20T02:43:33ZengNature PortfolioScientific Reports2045-23222024-12-0114111710.1038/s41598-024-81390-2An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinkingAnders J. Asp0Suelen Lucio Boschen1Su-Youne Chang2Jiwon Kim3Jodi L. Silvernail4J. Luis Lujan5Mayo Clinic Graduate School of Biomedical SciencesDepartment of Neurologic Surgery, Mayo ClinicDepartment of Neurologic Surgery, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurologic Surgery, Mayo ClinicDepartment of Neurologic Surgery, Mayo ClinicAbstract Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associated cost of approximately $249 billion annually in the U.S. alone. The effects of alcohol consumption are expected to increase significantly during the COVID-19 pandemic, with alcohol sales increasing by approximately 54%, potentially exacerbating health concerns and risk-taking behaviors. Unfortunately, existing pharmacological and behavioral therapies for AUD are associated with poor success rates, with approximately 40% of individuals relapsing within three years of treatment. Pre-clinical studies have shown that chronic alcohol consumption leads to significant changes in synaptic function within the dorsal medial striatum (DMS), one of the brain regions associated with AUD and responsible for mediating goal-directed behavior. Specifically, chronic alcohol consumption has been associated with hyperactivity of dopamine receptor 1 (D1) medium spiny neurons (MSN) and hypoactivity of dopamine receptor 2 (D1) MSNs within the DMS. Optogenetic, chemogenetic, and transgenic approaches have demonstrated that reducing the D1/D2 MSN signaling imbalance decreases alcohol self-administration in rodent models of AUD. Here, we present an electrical stimulation approach that uses ultra-low (≤ 1 Hz) frequency (ULF) spike-timing-dependent plasticity (STDP) in mouse models of AUD to reduce DMS D1/D2 MSN signaling imbalances by stimulating D1-MSN afferents into the GPi and ACC glutamatergic projections to the DMS in a time-locked stimulation sequence. Our data suggest that GPi/ACC ULF-STDP selectively decreases DMS D1-MSN hyperactivity leading to reduced alcohol consumption without evoking undesired affective behaviors using electrical stimulation rather than approaches requiring genetic modification. This work represents a step towards fulfilling the unmet need for a reliable method of treating severe AUD through cell-type-specific control with clinically available neuromodulation tools.https://doi.org/10.1038/s41598-024-81390-2 |
| spellingShingle | Anders J. Asp Suelen Lucio Boschen Su-Youne Chang Jiwon Kim Jodi L. Silvernail J. Luis Lujan An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking Scientific Reports |
| title | An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking |
| title_full | An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking |
| title_fullStr | An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking |
| title_full_unstemmed | An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking |
| title_short | An ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking |
| title_sort | ultra low frequency spike timing dependent plasticity based approach for reducing alcohol drinking |
| url | https://doi.org/10.1038/s41598-024-81390-2 |
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