Tyrosine Hydroxylase-positive Nucleus Accumbens Neurons Influence Delay Discounting in a Mouse T-maze Task.

Delay discounting (DD) is a phenomenon where individuals devalue a reward associated with a temporal delay, with the rate of devaluation being representative of impulsive-like behavior. Here we first sought to develop and validate a mouse DD task to study brain circuits involved in DD decision-making within short developmental time windows, given widespread evidence of developmental regulation of impulse control and risk-taking. We optimized a T-maze DD task for mice that enables training and DD trials within two weeks.

A rat model of operant negative reinforcement in opioid-dependent males and females.

Rationale And Objective: Avoidance of opioid withdrawal plays a key role in human opioid addiction. Here, we present a procedure for studying operant negative reinforcement in rats that was inspired by primate procedures where opioid-dependent subjects lever-press to prevent naloxone infusions.

Methods: In Experiment 1, we trained rats (n = 30, 15 females) to lever-press to escape and then avoid mild footshocks (0.

Male rodent perirhinal cortex, but not ventral hippocampus, inhibition induces approach bias under object-based approach-avoidance conflict.

Neural models of approach-avoidance (AA) conflict behavior and its dysfunction have focused traditionally on the hippocampus, with the assumption that this medial temporal lobe (MTL) structure plays a ubiquitous role in arbitrating AA conflict. We challenge this perspective by using three different AA behavioral tasks in conjunction with optogenetics, to demonstrate that a neighboring region in male rats, perirhinal cortex, is also critically involved but only when conflicting motivational values are associated with objects and not contextual information. The ventral hippocampus, in contrast, was found not to be essential for object-associated AA conflict, suggesting its preferential involvement in context-associated conflict.

Elucidating medial temporal and frontal lobe contributions to approach-avoidance conflict decision-making using functional MRI and the hierarchical drift diffusion model.

The prefrontal cortex (PFC) has long been associated with arbitrating between approach and avoidance in the face of conflicting and uncertain motivational information, but recent work has also highlighted medial temporal lobe (MTL) involvement. It remains unclear, however, how the contributions of these regions differ in their resolution of conflict information and uncertainty. We designed an fMRI paradigm in which participants approached or avoided object pairs that differed by motivational conflict and outcome uncertainty (complete certainty vs.

Parallel ventral hippocampus-lateral septum pathways differentially regulate approach-avoidance conflict.

The ability to resolve an approach-avoidance conflict is critical to adaptive behavior. The ventral CA3 (vCA3) and CA1 (vCA1) subfields of the ventral hippocampus (vHPC) have been shown to facilitate avoidance and approach behavior, respectively, in the face of motivational conflict, but the neural circuits by which this subfield-specific regulation is implemented is unknown. We demonstrate that two distinct pathways from these subfields to lateral septum (LS) contribute to this divergent control.

Cortico-Striatal Control over Adaptive Goal-Directed Responding Elicited by Cues Signaling Sucrose Reward or Punishment.

The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been associated with the expression of adaptive and maladaptive behavior elicited by fear-related and drug-associated cues. However, reported effects of mPFC manipulations on cue-elicited natural reward-seeking and inhibition thereof have been varied, with few studies examining cortico-striatal contributions in tasks that require adaptive responding to cues signaling reward and punishment within the same session. The current study aimed to better elucidate the role of mPFC and NAc subdivisions, and their functional connectivity in cue-elicited adaptive responding using a novel discriminative cue responding task.

The rodent medial prefrontal cortex and associated circuits in orchestrating adaptive behavior under variable demands.

Emerging evidence implicates rodent medial prefrontal cortex (mPFC) in tasks requiring adaptation of behavior to changing information from external and internal sources. However, the computations within mPFC and subsequent outputs that determine behavior are incompletely understood. We review the involvement of mPFC subregions, and their projections to the striatum and amygdala in two broad types of tasks in rodents: 1) appetitive and aversive Pavlovian and operant conditioning tasks that engage mPFC-striatum and mPFC-amygdala circuits, and 2) foraging-based tasks that require decision making to optimize reward.

Relationship between voluntary ethanol drinking and approach-avoidance biases in the face of motivational conflict: novel sex-dependent associations in rats.

Rationale: Aberrant approach-avoidance conflict processing may contribute to compulsive seeking that characterizes addiction. Exploration of the relationship between drugs of abuse and approach-avoidance behavior remains limited, especially with ethanol.

Objectives: To investigate the effects of voluntary ethanol consumption on approach-avoidance conflict behavior and to examine the potential approach/avoidance bias to predict drinking in male and female rats.

The ventral hippocampus CA3 is critical in regulating timing uncertainty in temporal decision-making.

Timing uncertainty is a critical component of temporal decision-making, as it determines the decision strategies that maximize reward rate. However, little is known about the biological substrates of timing uncertainty. In this study, we report that the CA3 subregion of the ventral hippocampus (vCA3), a relatively unexplored area in timing, is critical in regulating timing uncertainty that informs temporal decision making.

Perirhinal Cortex is Involved in the Resolution of Learned Approach-Avoidance Conflict Associated with Discrete Objects.

The rodent ventral and primate anterior hippocampus have been implicated in approach-avoidance (AA) conflict processing. It is unclear, however, whether this structure contributes to AA conflict detection and/or resolution, and if its involvement extends to conditions of AA conflict devoid of spatial/contextual information. To investigate this, neurologically healthy human participants first learned to approach or avoid single novel visual objects with the goal of maximizing earned points.

The ventral hippocampus is necessary for cue-elicited, but not outcome driven approach-avoidance conflict decisions: a novel operant choice decision-making task.

Approach-avoidance conflict is induced when an organism encounters a stimulus that carries both positive and negative attributes. Accumulating evidence implicates the ventral hippocampus (VH) in the detection and resolution of approach-avoidance conflict, largely on the basis of maze-based tasks assaying innate and conditioned responses to situations of conflict. However, its role in discrete trial approach-avoidance decision-making has yet to be elucidated.

Ventral hippocampus inactivation enhances the extinction of active avoidance responses in the presence of safety signals but leaves discrete trial operant active avoidance performance intact.

The acquisition of active avoidance (AA) behavior is typically aided by the presence of two signals-the warning signal, which predicts the future occurrence of an aversive event (e.g., shocks), and the safety signal, which is presented upon successful avoidance of oncoming shocks.

The hippocampus contributes to temporal duration memory in the context of event sequences: A cross-species perspective.

Although a large body of research has implicated the hippocampus in the processing of memory for temporal duration, there is an exigent degree of inconsistency across studies that obfuscates the precise contributions of this structure. To shed light on this issue, the present review article surveys both historical and recent cross-species evidence emanating from a wide variety of experimental paradigms, identifying areas of convergence and divergence. We suggest that while factors such as time-scale (e.

Exploring the interaction between approach-avoidance conflict and memory processing.

The medial temporal lobe (MTL) has been implicated in approach-avoidance (AA) conflict processing, which arises when a stimulus is imbued with both positive and negative valences. Notably, since the MTL has been traditionally viewed as a mnemonic brain region, a pertinent question is how AA conflict and memory processing interact with each other behaviourally. We conducted two behavioural experiments to examine whether increased AA conflict processing has a significant impact on incidental mnemonic encoding and inferential reasoning.

Double dissociation of learned approach-avoidance conflict processing and spatial pattern separation along the dorsoventral axis of the dentate gyrus.

The ventral portion of the rodent hippocampus (HPC; anterior in primates) has been implicated in the detection and resolution of approach-avoidance conflict, which arises when an organism encounters a stimulus that predicts both positive and negative outcomes. Previous work has found differential regulation of approach-avoidance conflict behavior by the CA3 and CA1 subfields, with inhibition of ventral CA3 increasing approach toward conflicting stimuli and inhibition of the ventral CA1 potentiating avoidance. Here, we sought to extend these findings by investigating the role of the dentate gyrus (DG), the input region of the HPC, in learned approach-avoidance conflict processing in rats.

Prelimbic and infralimbic cortical inactivations attenuate contextually driven discriminative responding for reward.

The infralimbic (IL) and prelimbic (PL) cortices of the medial prefrontal cortex (mPFC) have been shown to differentially control context-dependent behavior, with the PL implicated in the expression of contextually conditioned fear and drug-seeking, and the IL in the suppression of these behaviors. However, the roles of these subregions in contextually driven natural reward-seeking remain relatively underexplored. The present study further examined the functional dichotomy within the mPFC in the contextual control over cued reward-seeking, using a contextual biconditional discrimination (CBD) task.

Dissociative effects of dorsomedial striatum D1 and D2 receptor antagonism in the regulation of anxiety and learned approach-avoidance conflict decision-making.

The dorsal striatum is traditionally known for its role in sensorimotor integration. However, the dorsomedial striatum (DMS) has also been implicated in cost-benefit conflict processing, a role more readily attributed to the ventral striatum (VS), as a site of limbic-motor integration. We recently showed that dopaminergic D1 (D1R) and D2 receptors (D2R) in the VS exert dissociable control over cue-elicited approach-avoidance decision-making, in the presence of conflicting motivational stimuli.

Repeated Cocaine Exposure Attenuates the Desire to Actively Avoid: A Novel Active Avoidance Runway Task.

Drug addiction is a disorder in which drug seeking persists despite aversive consequences. While it is well documented in animal models of drug sensitization that repeated drug exposure enhances positive incentive motivation for drug and natural reinforcers, its effect on negative incentive motivation, defined here as the motivation to avoid a cued aversive outcome, remains an open question. In the present study, we designed a novel active avoidance (AA) runway paradigm to assess the effects of repeated cocaine exposure on the to avoid an aversive outcome.

Dissociable roles of the nucleus accumbens D1 and D2 receptors in regulating cue-elicited approach-avoidance conflict decision-making.

Rationale: Approach and avoidance decisions are made when an animal experiences a state of motivational conflict inflicted by stimuli imbued with both positive and negative valences. The nucleus accumbens (NAc), a site where valenced information and action selection converge, has recently been found to be critically involved in the resolution of approach-avoidance conflict. However, the individual roles of the region's dopamine receptor D1 (D1R)- and D2 (D2R)-expressing medium spiny neurons (MSNs) in regulating conflict resolution have not been well established.

Ventral Hippocampal CA1 and CA3 Differentially Mediate Learned Approach-Avoidance Conflict Processing.

Approach-avoidance conflict arises when an animal encounters a stimulus that is associated simultaneously with positive and negative valences [1]. The effective resolution of approach-avoidance conflict is critical for survival and is believed to go awry in a number of mental disorders, such as anxiety and addiction. An accumulation of evidence from both rodents and humans suggests that the ventral hippocampus (anterior in humans) plays a key role in approach-avoidance conflict processing [2-8], with one influential model proposing that this structure modulates behavioral inhibition in the face of conflicting goals by increasing the influence of negative valences [9].

Ventral, but not dorsal, hippocampus inactivation impairs reward memory expression and retrieval in contexts defined by proximal cues.

The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well-established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal-based contextual memory processing in appetitively motivated tasks.

Caudal Nucleus Accumbens Core Is Critical in the Regulation of Cue-Elicited Approach-Avoidance Decisions.

The nucleus accumbens (NAc) is thought to be a site of integration of positively and negatively valenced information and action selection. Functional differentiation in valence processing has previously been found along the rostrocaudal axis of the shell region of the NAc in assessments of unconditioned motivation. Given that the core region of the NAc has been implicated in the elicitation of motivated behavior in response to conditioned cues, we sought to assess the role of caudal, intermediate, and rostral sites within this subregion in cue-elicited approach-avoidance decisions.

The role of the hippocampus in approach-avoidance conflict decision-making: Evidence from rodent and human studies.

The hippocampus (HPC) has been traditionally considered to subserve mnemonic processing and spatial cognition. Over the past decade, however, there has been increasing interest in its contributions to processes beyond these two domains. One question is whether the HPC plays an important role in decision-making under conditions of high approach-avoidance conflict, a scenario that arises when a goal stimulus is simultaneously associated with reward and punishment.

Different dosing regimens of repeated ketamine administration have opposite effects on novelty processing in rats.

Repeated exposure to sub-anesthetic doses of ketamine in rats has been shown to induce cognitive deficits, as well as behavioral changes akin to the negative symptoms of schizophrenia, giving much face validity to the use of ketamine administration as a pharmacological model of schizophrenia. This study sought to further characterize the behavioral effects of two different ketamine pre-treatment regimens, focusing primarily on the effects of repeated ketamine administration on novelty processing, a capacity that is disrupted in schizophrenia. Rats received 5 or 14 intra-peritoneal injections of 30mg/kg ketamine or saline across 5 or 7days, respectively.