Biology subjects

Wiener, S. I.

Publications and source records attributed to Wiener, S. I..

3 recordsLinked to original sources

bioRxiv2022

Activation of prefrontal cortex and striatal regions in rats after shifting between rules in a T-maze

Prefrontal cortical and striatal areas have been identified by inactivation or lesion studies to be required for behavioral flexibility, including selecting and processing of different types of information. In order to identify these networks activated selectively during acquisition of new reward contingency rules, rats were trained to discriminate orientations of bars presented in pseudo-random sequence on two video monitors positioned behind the goal sites on a T maze with return arms. A second group already trained in the visual discrimination task learned to alternate left and right goal arm visits in the same maze while ignoring the visual cues still being presented. In each experimental group, once the rats reached criterion performance, the brains were prepared after a 90 minute delay, for later processing for c-fos immunohistochemistry. While both groups extinguished a prior strategy and acquired a new rule, they differed by the identity of the strategies, and previous learning experience. Among the 28 forebrain areas examined, there were significant increases in the relative density of c-fos immunoreactive cell bodies after learning the second rule in prefrontal cortex cingulate, prelimbic and infralimbic areas, in dorsomedial striatum and the core of nucleus accumbens, in ventral subiculum, and the central nucleus of the amygdala. These largely correspond to structures anatomically identified by previous inactivation studies. The data suggest that this dynamic network may underlie reward-based selection for action, a type of cognitive flexibility.

neuroscience↗

bioRxiv2022

Locus c{oelig}ruleus noradrenergic neurons phase-lock to prefrontal cortical and hippocampal infra-slow rhythms which synchronize with behavioral events

The locus cruleus (LC) is the primary source of noradrenergic projections to the forebrain, and, in prefrontal cortex, is implicated in decision-making and executive function. LC neurons phase-lock to cortical infra-slow wave oscillations during sleep. Such infra-slow rhythms are rarely reported in awake states, despite their interest, since they correspond to the time scale of behavior. Thus, we investigated LC neuronal synchrony with infra-slow rhythms in awake rats performing an attentional set-shifting task. Local field potential (LFP) oscillation cycles in prefrontal cortex and hippocampus on the order of 0.4 Hz phase-locked to task events at crucial maze locations. Indeed, successive cycles of the infra-slow rhythms showed different wavelengths, as if they are periodic oscillations that can reset phase relative to salient events. Simultaneously recorded infra-slow rhythms in prefrontal cortex and hippocampus could show different cycle durations as well suggesting independent control. Most LC neurons (including optogenetically identified noradrenergic neurons) recorded here were phase-locked to these infra-slow rhythms, as were hippocampal and prefrontal units recorded on the LFP probes. The infra-slow oscillations also phase-modulated gamma amplitude, linking these rhythms at the time scale of behavior to those coordinating neuronal synchrony. This would provide a potential mechanism where noradrenaline, released by LC neurons in concert with the infra-slow rhythm, would facilitate synchronization or reset of these brain networks, underlying behavioral adaptation.

neuroscience↗

bioRxiv2021

Post-trauma behavioral phenotype predicts vulnerability to fear relapse after extinction

Current treatments for trauma-related disorders remain ineffective for many patients. Here, we modeled interindividual differences in post-therapy fear relapse with a novel ethologically relevant trauma recovery paradigm. After traumatic fear conditioning, male rats underwent fear extinction while foraging in a large enriched arena, permitting the expression of a wide spectrum of behaviors, assessed by an automated pipeline. This multidimensional behavioral assessment revealed that post-conditioning fear response profiles clustered into two groups, respectively characterized by active vs. passive fear responses. After trauma, some animals expressed fear by freezing, while others darted, as if fleeing from danger. Remarkably, belonging to the darters or freezers group predicted differential levels of vulnerability to fear relapse after extinction. Moreover, genome-wide transcriptional profiling revealed that these groups differentially regulated specific sets of genes, some of which have previously been implicated in anxiety and trauma-related disorders. Our results suggest that post-trauma behavioral phenotypes and the associated epigenetic landscapes can serve as markers of fear relapse susceptibility, and thus may be instrumental for future development of more effective treatments for psychiatric patients.

neuroscience↗