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Wiener, S. I.

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

7 recordsLinked to original sources

A novel critic signal in identified midbrain dopaminergic neurons of mice training inoperant tasks

Classically, midbrain dopaminergic neuron activity is triggered by unexpected rewards, then, upon learning, by reward-predictive conditioned stimuli. When expected rewards are withheld, firing is inhibited. This activity occurs too late to directly affect the neuronal circuitry underlying decision-making, inspiring the development of temporal difference (TD) reinforcement learning models. To test for more timely critical feedback during decision-making and learning, we recorded optogenetically identified dopaminergic, putative GABAergic and other neurons of the ventral tegmental area (VTA) and substantia nigra pars compacta in mice training in visual and olfactory discrimination tasks. The mice often adhered to unrewarded and untrained task strategies (e.g., spatial alternation) rather than making random choices. In order to probe for reward/punishment predictive activity, a delay was imposed between nose-poke choices and signals for reward or punishment. As animals performed below criterion levels, dopaminergic and other neurons firing rates signaled correct versus incorrect choices immediately after choices, but prior to the onset of trial outcome signals. Thus, this activity signaled the rewarded rule even as the mice performed other unrewarded strategies. Putative GABAergic neurons fired during nose-poke choices, potentially reducing network activity prior to reward prediction signals. This reward predictive activity could serve as a critic signal expressed immediately after choices are made, priming the network for canonical DA reward/punishment activity, facilitating network functional modifications. This is consistent with a role for dopamine in arbitration between brain modules to choose among diverse strategies during goal-directed behavior. These findings suggest extensions of theoretical formulations interpreting dopaminergic neuronal activity. Significance statementModels of dopaminergic influence on circuit modifications during learning evoke mechanisms dealing with the delay between neural activity leading up to choices, and when the reinforcing outcome actually occurs. Here, as mice trained in sensory discrimination tasks with a delay between behavioral responses and reinforcement signals, they performed several unrewarded behavioral strategies. Simultaneously, dopaminergic nuclei neurons instead reflected the current task rule, predicting whether the choice was correct or not, providing an immediate "critic" signal prior to canonical trial outcome signals. This provides evidence for brain mechanisms to overcome innate or acquired habits to perform behaviors optimizing positive outcomes.

neuroscience↗

Detection of cell assemblies in high-density extracellular electrophysiological recordings

Cell assemblies, i.e., concurrently active groups of neurons, likely underlie neural processing for higher brain functions. Recent technological progress has enabled large-scale recording of neuronal activity, permitting the exploration and analysis of cell assembly dynamics. This review aims to provide both conceptual insights and practical knowledge pertaining to principal methodologies used for detecting cell assemblies in the last fifteen years. The goal is to assist readers in selecting and comparing various protocols to optimize their data processing and analysis pipeline. Each algorithm is explained with its fundamental principles, their application in neuroscience for cell assembly detection, and illustrated with published studies. Recognizing the similarities, advantages, and drawbacks of diverse methodologies may pave the way for developing new procedures for cell assembly identification to facilitate future endeavors in the understanding of brain activity.

neuroscience↗

Differential encoding of fear learning and fear expression in the ventral and dorsal hippocampus

Classically, the dorsal and ventral hippocampus are thought to play distinct roles in fear conditioning, with the dorsal hippocampus primarily handling information about environmental cues and contexts, and the ventral hippocampus more involved in emotional processing. Both functions are essential for the learning and expression of conditioned fear responses, but how these processes are integrated remains largely unexplored. In this study, we simultaneously recorded single-unit activity from the dorsal and ventral hippocampus during fear conditioning to identify the neural dynamics that may underlie these processes and their integration. As fear expression emerged, shifts in neural firing patterns were observed in both regions, with a stronger shift in ventral hippocampal activity, as expected. However, contrary to the prevailing view of the ventral hippocampus as central to anxiety and fear regulation, fear expression-related neuronal responses were surprisingly more predominant in the dorsal hippocampus. In contrast, ventral hippocampal neuronal activity was more closely linked with the acquisition of conditioned fear. These features were combined in cell assemblies that emerged during fear conditioning, composed of both dorsal fear expression-responsive neurons and ventral fear learning-responsive cells. These multifactorial engrams, distributed along the hippocampal dorso-ventral axis, provide a potential substrate for integrating fear acquisition and expression, thereby coordinating associative learning.

neuroscience↗

Rat anterior cingulate neurons responsive to rule or strategy changes are modulated by the hippocampal theta rhythm and sharp-wave ripples

To better understand neural processing during adaptive learning of stimulus-response-reward contingencies, we recorded synchrony of neuronal activity in anterior cingulate cortex (ACC) with hippocampal rhythms in male rats acquiring and switching between spatial and visual discrimination tasks in a Y-maze. ACC population and single unit activity responded shortly after task rule changes, or just before the rats adopted different task strategies. Hippocampal theta oscillations (associated with memory encoding) modulated an elevated proportion of rule-change responsive neurons (70%), but other neurons that were correlated with strategy-change, strategy value, and reward-rate were not. However, hippocampal sharp wave-ripples modulated significantly higher proportions of rule-change, strategy-change and reward-rate responsive cells during post-session sleep but not pre-session sleep. This suggests an underestimated mechanism for hippocampal mismatch and contextual signals to facilitate ACC detection of contingency changes for cognitive flexibility, a function that is attenuated after it is damaged.

neuroscience↗

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↗

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↗

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↗