Biology subjects

Stout, J. J.

Publications and source records attributed to Stout, J. J..

3 recordsLinked to original sources

bioRxiv2024

Deliberative Behaviors and Prefrontal-Hippocampal Coupling are Disrupted in a Rat Model of Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASDs) are characterized by a range of physical, cognitive, and behavioral impairments. Determining how temporally specific alcohol exposure (AE) affects neural circuits is crucial to understanding the FASD phenotype. Third trimester AE can be modeled in rats by administering alcohol during the first two postnatal weeks, which damages the medial prefrontal cortex (mPFC), thalamic nucleus reuniens, and hippocampus (HPC), structures whose functional interactions are required for working memory and executive function. Therefore, we hypothesized that AE during this period would impair working memory, disrupt choice behaviors, and alter mPFC-HPC oscillatory synchrony. To test this hypothesis, we recorded local field potentials from the mPFC and dorsal HPC as AE and sham intubated (SI) rats performed a spatial working memory task in adulthood and implemented algorithms to detect vicarious trial and errors (VTEs), behaviors associated with deliberative decision- making. We found that, compared to the SI group, the AE group performed fewer VTEs and demonstrated a disturbed relationship between VTEs and choice outcomes, while spatial working memory was unimpaired. This behavioral disruption was accompanied by alterations to mPFC and HPC oscillatory activity in the theta and beta bands, respectively, and a reduced prevalence of mPFC-HPC synchronous events. When trained on multiple behavioral variables, a machine learning algorithm could accurately predict whether rats were in the AE or SI group, thus characterizing a potential phenotype following third trimester AE. Together, these findings indicate that third trimester AE disrupts mPFC-HPC oscillatory interactions and choice behaviors. Significance statementFetal alcohol spectrum disorders (FASDs) occur at an alarmingly high rate worldwide. Prenatal alcohol exposure leads to significant perturbations in brain circuitry that are accompanied by cognitive deficits, including disrupted executive functioning and working memory. These deficits stem from structural changes within several key brain regions including the prefrontal cortex, thalamic nucleus reuniens, and hippocampus. To better understand the cognitive deficits observed in FASD patients, we employed a rodent model of alcohol exposure during the third trimester, a period when these regions are especially vulnerable to alcohol-induced damage. We show that alcohol exposure disrupts choice behaviors and prefrontal-hippocampal functional connectivity during a working memory task, identifying the prefrontal-hippocampal network as a potential therapeutic target in FASD treatment.

neuroscience↗

bioRxiv2023

Harnessing prefrontal-hippocampal theta synchrony to enhance memory-guided choice

Functional interactions between the prefrontal cortex and hippocampus, as revealed by strong oscillatory synchronization in the theta (6-11 Hz) frequency range, correlate with memory-guided decision-making. However, the degree to which this form of long-range synchronization influences memory-guided choice remains unclear. We developed a brain machine interface that initiated task trials based on the magnitude of prefrontal hippocampal theta synchronization, then measured choice outcomes. Trials initiated based on strong prefrontal-hippocampal theta synchrony were more likely to be correct compared to control trials on both working memory-dependent and -independent tasks. Prefrontal-thalamic neural interactions increased with prefrontal-hippocampal synchrony and optogenetic activation of the ventral midline thalamus primarily entrained prefrontal theta rhythms, but dynamically modulated synchrony. Together, our results show that prefrontal-hippocampal theta synchronization leads to a higher probability of a correct choice and strengthens prefrontal-thalamic dialogue. Our findings reveal new insights into the neural circuit dynamics underlying memory-guided choices and highlight a promising technique to potentiate cognitive processes or behavior via brain machine interfacing.

neuroscience↗

bioRxiv2021

The Ventral Midline Thalamus Mediates Successful Deliberation by Coordinating Prefrontal and Hippocampal Neural Activity

When faced with difficult choices, the possible outcomes are considered through a process known as deliberation. In rats, deliberation can be reflected by pause-and-reorienting behaviors, better known as Vicarious Trial and Errors (VTEs). While VTEs are thought to require medial prefrontal cortex (mPFC) and dorsal hippocampal (dHPC) interactions, no work has demonstrated such a dual requirement. The nucleus reuniens (Re) of the ventral midline thalamus is anatomically connected with both the mPFC and dHPC, is required for HPC-dependent spatial memory tasks, and is critical for mPFC-dHPC neural synchronization. Currently, it is unclear if, or how, the Re is involved in deliberation. Therefore, by examining the role of the Re on VTE behaviors, we can better understand the anatomical and physiological mechanisms supporting deliberation. Here, we examined the impact of Re suppression on VTE behaviors and mPFC-dHPC theta synchrony during well-learned performance of a HPC-dependent delayed alternation (DA) task. Pharmacological suppression of the Re increased VTE behaviors that resulted in erroneous choices. These errors were best characterized as perseverative behaviors, where at the decision-point, some rats repeatedly turned in the direction that previously yielded no reward, while simultaneously deliberating. These failed deliberations were associated with a reduction in mPFC-dHPC theta coherence at the choice-point. Importantly, the reduction in mPFC-dHPC theta synchrony observed during VTE behaviors was almost entirely driven by Re-suppression induced changes to the mPFC theta oscillation. Our findings suggest that the Re is important for successful deliberation, and mPFC-dHPC interactions, by coordinating local theta oscillations in the mPFC.

neuroscience↗