scholarly journals An ultra-low frequency spike timing dependent plasticity-based approach for treating alcohol use disorder

2021 ◽  
Author(s):  
Anders J Asp ◽  
Suelen Lucio Boschen ◽  
J Luis Lujan
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Dopamine Receptor ◽  
Alcohol Use Disorder ◽  
Spike Timing ◽  
Synaptic Function ◽  
Chronic Alcohol ◽  
Spike Timing Dependent Plasticity ◽  
Chronic Alcohol Consumption ◽  
Dependent Plasticity

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 increased by approximately 54%, potentially exacerbating health concerns and risk-taking behaviors. Unfortunately, existing pharmacological and behavioral therapies for AUD have historically been 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. However, these approaches cannot be studied clinically at this time. Here, we present an electrical stimulation alternative that uses ultra-low (<=1Hz) frequency (ULF) spike-timing dependent plasticity (STDP) 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 in a two-bottle choice mouse model of AUD.

scholarly journals Chronic Alcohol Use and Accompanying Noncommunicable Diseases

2020 ◽  
Vol 4 (2) ◽  
pp. 227-242
Author(s):  
Israel Oluwasegun Ayenigbara
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Narrative Review ◽  
Background Information ◽  
Noncommunicable Diseases ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
Vitamin Deficiencies ◽  
Immune System Dysfunction ◽  
Gastrointestinal Problems

Introduction. Heavy and chronic alcohol use connotes frequent, continuous and persistent consumption of alcoholic drinks over an extended period of time. Importantly, heavy consumption of alcohol causes many health problems to the drinker and the society at large, as over 5.1% of the global burden of morbidity and injuries are attributable to alcohol usage alone. Aim. The purpose of this study is to identify some of the noncommunicable diseases that are associated with chronic alcohol consumption through a systematic and narrative review, with detailed descriptions of the occurrences. Methods. A systematic and narrative review of literature that evaluates noncommunicable diseases associated with chronic alcohol consumption was carried out using Google, Medline and databases of major international health organizations. Keywords used as search terms were alcoholism, chronic alcohol use and heavy alcohol use; these terms were matched with occurrences and risk of noncommunicable diseases. Studies included in this review are clinical trials, meta-analyses, randomized controlled trials, and systematic and review articles. Results. The findings revealed that chronic alcohol use is either a single or joint risk factor for Alzheimer’s disease and dementia, arthritis, brain malfunction, cancer (most commonly of the oropharynx, larynx, oesophagus, liver, colon, rectum or breast), chronic obstructive pulmonary disease (COPD), diabetes, epilepsy, heart diseases and cardiovascular diseases, immune system dysfunction, malnourishment and vitamin deficiencies, mood disorders, bipolar disorder and depression, osteoporosis and bone malformation, pancreatitis, and ulcers and gastrointestinal problems. Conclusion. These findings are background information as they revealed some of the noncommunicable diseases associated with chronic alcohol use. Hence, more and precise long-term cohort studies are necessary for a better understanding of the occurrences and epidemiology of noncommunicable diseases as a result of chronic alcohol use.

Stable Competitive Dynamics Emerge from Multispike Interactions in a Stochastic Model of Spike-Timing-Dependent Plasticity

2006 ◽  
Vol 18 (10) ◽  
pp. 2414-2464 ◽  
Author(s):  
Peter A. Appleby ◽  
Terry Elliott
Keyword(s):  
Synaptic Plasticity ◽  
Stochastic Model ◽  
Higher Order ◽  
Spike Timing ◽  
Competitive Dynamics ◽  
Spike Timing Dependent Plasticity ◽  
Interaction Function ◽  
Dependent Plasticity ◽  
Order Interaction ◽  
Synaptic Dynamics

In earlier work we presented a stochastic model of spike-timing-dependent plasticity (STDP) in which STDP emerges only at the level of temporal or spatial synaptic ensembles. We derived the two-spike interaction function from this model and showed that it exhibits an STDP-like form. Here, we extend this work by examining the general n-spike interaction functions that may be derived from the model. A comparison between the two-spike interaction function and the higher-order interaction functions reveals profound differences. In particular, we show that the two-spike interaction function cannot support stable, competitive synaptic plasticity, such as that seen during neuronal development, without including modifications designed specifically to stabilize its behavior. In contrast, we show that all the higher-order interaction functions exhibit a fixed-point structure consistent with the presence of competitive synaptic dynamics. This difference originates in the unification of our proposed “switch” mechanism for synaptic plasticity, coupling synaptic depression and synaptic potentiation processes together. While three or more spikes are required to probe this coupling, two spikes can never do so. We conclude that this coupling is critical to the presence of competitive dynamics and that multispike interactions are therefore vital to understanding synaptic competition.

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