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

Abstract

Background: Although 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.Methods: LFP 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 × 2 recordings/rat) and during sessions of limited access to alcohol (n = 5/sex × 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 with oscillation data 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. Results: Our 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. Conversely, females in estrus drank very 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. Conclusions: The 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.

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

“…LFP oscillation analysis: Similar to our previous publications [20,21,22] we built general linear models to classify rats based on group assignment (i.e., control, MIA, AE, or Dual) using LFP oscillation data. Since each rat underwent two baseline recording sessions, we used data from both sessions to build baseline models.…”

“…Model performance is reported as mean area under the receiver operating characteristic curve (AUC) ± 95% confidence interval. Because we used multiple recording sessions from the same animal and 5-second bins as samples, we also evaluated models built on permutations of binary rat groupings ("animal detector"), as previously described [22]. This was done by keeping the LFP oscillation data together with the rat it was recorded from, and shuffling the group assignment of each rat's set of recordings.…”

“…Electrodes were designed and constructed in-house and were similar to those used in our previous publications [20,21,22]. Animals were anesthetized with isoflurane gas (4% induction, 2% maintenance) and mounted in a stereotaxic frame.…”

“…Data from each recording were analyzed using frequency ranges from the rodent literature (δ =1-4 Hz, θ = 5-10 Hz, α = 11-14 Hz, β = 15-30 Hz, low γ = 45-65 Hz, and high γ = 70-90 Hz). LFP signal processing to characterize the power spectral densities (PSD) within, and coherence between brain regions, for each rat was calculated using custom code written for Matlab, as we have previously published [20,21,22]…”

“…CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It Electrodes were designed and constructed in-house and were similar to those used in our previous publications [20,21,22]. Animals were anesthetized with isoflurane gas (4% induction, 2% maintenance) and mounted in a stereotaxic frame.…”