Biology subjects

Dwiel, L. L.

Publications and source records attributed to Dwiel, L. L..

3 recordsLinked to original sources

bioRxiv2022

Maternal immune activation and adolescent alcohol exposure increases alcohol drinking and disrupts cortical-striatal-hippocampal oscillations in adult offspring

Maternal immune activation (MIA) is strongly associated with an increased risk of developing mental illness in adulthood, which often co-occurs with alcohol misuse. The current study aimed to begin to determine whether MIA, combined with adolescent alcohol exposure (AE), could be used as a model with which we could study the neurobiological mechanisms behind such co-occurring disorders. Pregnant Sprague-Dawley rats were treated with PolyI:C or saline on gestational day 15. Half of the offspring were given continuous access to alcohol during adolescence, leading to four experimental groups: controls, MIA, AE, and Dual (MIA + AE). We then evaluated whether MIA and/or AE alters: 1) alcohol consumption; and 2) cortical-striatal-hippocampal oscillations in adult offspring. Dual rats, particularly females, drank significantly more alcohol in adulthood compared to all other groups. Using machine learning to build predictive models from oscillations, we were able to differentiate Dual rats from control rats and AE rats in both sexes, and Dual rats from MIA rats in females. The current data suggest that MIA+AE (Dual "hits") is a valuable model that we can use to study the neurobiological underpinnings of co-occurring disorders. Our future work aims to extend these findings to other addictive substances to enhance the translational relevance of this model.

neuroscience↗

bioRxiv2019

Sex differences in the ability of corticostriatal oscillations to predict rodent alcohol consumption

BackgroundAlthough male and female rats differ in their patterns of alcohol use, little is known regarding the neural circuit activity that underlies these differences in behavior. The current study used a machine learning approach to characterize sex differences in local field potential (LFP) oscillations that may relate to sex differences in alcohol drinking behavior.\n\nMethodsLFP oscillations were recorded from the nucleus accumbens shell and the rodent medial prefrontal cortex of adult male and female Sprague-Dawley rats. Recordings occurred before rats were exposed to alcohol (n=10/sex X 2 recordings/rat) and during sessions of limited access to alcohol (n=5/sex X 5 recordings/rat). Oscillations were also recorded from each female rat in each phase of estrous prior to alcohol exposure. Using machine-learning, we built predictive models to classify rats based on: 1) biological sex; 2) phase of estrous; and 3) alcohol intake levels. We evaluated model performance from real data by comparing it to the performance of models built and tested on permutations of the data.\n\nResultsOur data demonstrate that corticostriatal oscillations were able to predict alcohol intake levels in males (p<0.01), but not in females (p=0.45). The accuracies of models predicting biological sex and phase of estrous were related to fluctuations observed in alcohol drinking levels; females in diestrus drank more alcohol than males (p=0.052), and the male vs. diestrus female model had the highest accuracy (71.01%) compared to chance estimates.\n\nConversely, females in estrus drank similar amounts of alcohol to males (p=0.702), and the male vs. estrus female model had the lowest accuracy (56.14%) compared to chance estimates.\n\nConclusionsThe current data demonstrate that oscillations recorded from corticostriatal circuits contain significant information regarding alcohol drinking in males, but not alcohol drinking in females. Future work will focus on identifying where to record LFP oscillations in order to predict alcohol drinking in females, which may help elucidate sex-specific neural targets for future therapeutic development.

neuroscience↗

bioRxiv2018

Identifying neural predictors of response to cortical or striatal deep brain stimulation in a rodent model of alcohol drinking: Towards developing individualized therapies for alcohol use disorders

Individuals differ in their vulnerability to develop alcohol dependence that are determined by innate and environmental factors. The corticostriatal circuit is heavily involved in the development of alcohol dependence and may contain neural information regarding vulnerability to drink excessively. In the current experiment, we hypothesized that we could characterize high and low alcohol-drinking rats (HD and LD, respectively) based on corticostriatal oscillations, and that these subgroups would differentially respond to corticostriatal brain stimulation. Rats were trained to drink 10% alcohol in a limited access paradigm. In separate sessions, local field potentials (LFPs) were recorded from the nucleus accumbens shell (NAcSh) and medial prefrontal cortex (mPFC) of male Sprague-Dawley rats (n=13). Based on training alcohol consumption levels, we classified rats using a median split as HD or LD. Then, using machine-learning, we built predictive models to classify rats as HD or LD by corticostriatal LFPs and compared the model performance from real data to the performance of models built on data permutations. Additionally, we explored the impact of NAcSh or mPFC stimulation on alcohol consumption in HD vs. LD. Corticostriatal LFPs were able predict HD vs. LD group classification with greater accuracy than expected by chance (>80% accuracy). Additionally, NAcSh stimulation significantly reduced alcohol consumption in HD, but not LD (p<0.05), while mPFC stimulation did not alter drinking behavior in either HD or LD (p>0.05). These data collectively show that the corticostriatal circuit is differentially involved in regulating alcohol intake in HD vs. LD rats, and suggests that corticostriatal activity may have the potential to predict a vulnerability to develop alcohol dependence in a clinical population.

neuroscience↗