Current Opinion in Behavioral Sciences

Recent evidence demonstrates that new events are learned in the context of their relationships to existing memories. Within the hippocampus and medial prefrontal cortex, related memories are represented by integrated codes that connect events experienced at different times and places. Integrated codes form the basis of spatial, temporal, and conceptual maps of experience. These maps represent information that goes beyond direct experience and support generalization behaviors that require knowledge be used in new ways...

Rational analyses of memory suggest that retrievability of past experience depends on its usefulness for predicting the future: memory is adapted to the temporal structure of the environment. Recent research has enriched this view by applying it to semantic memory and reinforcement learning. This paper describes how multiple forms of memory can be linked via common predictive principles, possibly subserved by a shared neural substrate in the hippocampus. Predictive principles offer an explanation for a wide range of behavioral and neural phenomena, including semantic fluency, temporal contiguity effects in episodic memory, and the topological properties of hippocampal place cells...

Theories of episodic memory have long hypothesized that recollection of a specific instance from one's life is mediated by recovery of a neural state of spatiotemporal context. This paper reviews recent theoretical advances in formal models of spatiotemporal context and a growing body of neurophysiological evidence from human imaging studies and animal work that neural populations in the hippocampus and other brain regions support a representation of spatiotemporal context.

There is considerable recent evidence that, in addition to its representation of space, the hippocampus also represents the temporal organization of memories. Time plays a central role in episodic memory, and studies have identified the hippocampus as playing an essential role in the temporal organization of memories in humans and animals. Temporal organization is supported by a gradually changing temporal context signal in the hippocampus, and this changing context signal involves "time cells" in the hippocampus that code sequential moments in temporally organized experiences...

No abstract text is available yet for this article.

Understanding the neural mechanisms of risky decision-making is critical to developing appropriate treatments for psychiatric disorders, problem gambling, and addiction to drugs of abuse. Probing neurobiological mechanisms requires the use of nonhuman animal models (particularly rhesus macaques, rats, and mice). However, there is considerable variation across species in risk preferences. Nevertheless, there are shared core features of risky decision-making present across species. As demonstrated with a wide variety of behavioral paradigms, modulators of risk preference observed in humans are readily replicated in model species...

In this review, we examine the paradigms and measures available for experimentally studying mixed emotions in the laboratory. For eliciting mixed emotions, we describe a mixed emotions film library that allows for the repeated elicitation of a specific homogeneous mixed emotional state and appropriately matched pure positive, pure negative, and neutral emotional states. For assessing mixed emotions, we consider subjective and objective measures that fall into univariate, bivariate, and multivariate measurement categories...

Individual differences in temperament are associated with psychopathology in humans. Moreover, the relationship between temperament and anxiety-, depression-, PTSD- and addiction-related behaviors can be modeled in animals. This review will highlight these relationships with a focus on individual differences in the response to stressors, fear conditioning and drugs of abuse using animals that differ in their response to a novel environment. We will discuss behavioral and neurobiological commonalities amongst these behaviors with a focus on the hippocampus and, in particular, growth factors as promising novel targets for therapeutic intervention...

Post-traumatic stress disorder (PTSD) is characterized by persistent re-experiencing of a traumatic event, avoidance, and increased arousal. The approved pharmacological treatments for PTSD have limited efficacy (~60% treatment response), supporting the need for identification of biomarkers and novel pharmacological therapies. Mounting evidence suggests increased inflammatory markers and altered immune gene expression correlate with the severity of symptoms in PTSD patients. However a causal role of immune signaling in development and maintenance of PTSD symptoms is not clear, as inflammation may also be an epiphenomenon related to metabolic and behavioral effects of stress...

In major depressive disorder, women exhibit higher lifetime prevalence and different antidepressant response rates than men, which illustrates the importance of examining individual differences in the pathophysiology of depression and therapeutic response. In recent years, the consideration of sex in related preclinical research has thus gained interest-particularly in light of novel evidence for rapid-acting antidepressants. Notably, the literature recently revealed a higher sensitivity of females to the antidepressant effects of the N-methyl-D-aspartate receptor antagonist ketamine, in both baseline and preclinical conditions...

Adverse early-life experiences, including various forms of early-life stress, have consistently been linked with vulnerability to cognitive and emotional disorders later in life. Understanding the mechanisms underlying the enduring consequences of early-life stress is an active area of research, because this knowledge is critical for developing potential interventions. Animal models of early-life stress typically rely on manipulating maternal/parental presence and care, because these are the major source of early-life experiences in humans...

Young infant rat pups learn to approach cues associated with pain rather than learning amygdala-dependent fear. This approach response is considered caregiver-seeking and ecologically relevant within the context of attachment. With maturation, increases in the stress hormone corticosterone permit amygdala-dependent fear, which is crucial for survival during independent living. During the developmental transition from attachment to fear learning, maternal presence suppresses corticosterone elevation to block amygdala-dependent fear learning and re-engage the attachment circuitry...

A wide range of stressful experiences can influence human decision making in complex ways beyond the simple predictions of a fight-or-flight model. Recent advances may provide insight into this complicated interaction, potentially in directions that could result in translational applications. Early research suggests that stress exposure influences basic neural circuits involved in reward processing and learning, while also biasing decisions towards habit and modulating our propensity to engage in risk-taking...

Psychiatric diseases, notably major depression, are associated with imbalance of excitatory and inhibitory neurotransmission within the prefrontal cortex (PFC) and related limbic brain circuitry. In many cases these illnesses are precipitated or exacerbated by chronic stress, which also alters excitatory and inhibitory neurotransmitter systems. Notably, exposure to repeated uncontrollable stress causes persistent changes in the synaptic integrity and function of the principal glutamatergic excitatory neurons in the PFC, characterized by neuronal atrophy and loss of synaptic connections...

Youth with family history (FH+) of substance use disorders (SUDs) are at increased risk for developing SUDs. Similarly, childhood attention deficit hyperactivity disorder (ADHD) is considered to be a risk factor for developing SUDs. Recent research has suggested a close association between SUDs and impaired inhibitory control. As such, it is crucial to examine common and distinct neural alterations associated with inhibitory control in these at-risk groups, particularly prior to the initiation of heavy substance use...

Cues in the environment can guide behavior in adaptive ways, leading one towards valuable resources such as food, water, or a potential mate. However, cues in the environment may also serve as powerful motivators that lead to maladaptive patterns of behavior, such as addiction. Importantly, and central to this article, there is considerable individual variation in the extent to which reward cues gain motivational control over behavior. Here we describe an animal model that captures this individual variation, allowing us to better understand the psychological and neurobiological processes that contribute to cue-evoked behaviors...

Many reports show that repeated cocaine administration increases dendritic spine density in medium spiny neurons of the nucleus accumbens, but there is less agreement regarding the persistence of these changes. In this review we examine these discrepancies by systematically categorizing papers that measured cocaine-induced changes in accumbal spine density. We compare published reports based on withdrawal time, short versus long duration of cocaine administration, environmental pairing with cocaine, and core/shell subregion specificity...

Fundamental to cognitive models of addiction is the gradual strengthening of automatic, urge-related responding that develops in tandem with the diminution of self-control-related processes aimed at inhibiting impulses. Recent conceptualizations of addiction also include a third set of cognitive processes related to self-awareness and superordinate regulation of self-control and other higher brain function. This review describes new human research evidence and theoretical developments related to the multicausal strengthening of urge-related responding and failure of self-control in addiction, and the etiology of disrupted self-awareness and rational decision-making associated with continued substance use...

The transition from moderate to compulsive alcohol drinking is driven by increasingly dysfunctional reward and stress systems. We review behavioral and pharmacological studies of alcohol self-administration in rats that were mainly conducted within the framework of the alcohol vapor model of dependence. We discuss neurotransmitter systems that are implicated in alcohol drinking, with a focus on contrasting those neurotransmitter systems that drive behavior in the dependent vs. nondependent states. We hypothesize that the identification of systems that become increasingly dysfunctional in alcohol dependence will reveal possible targets for successful interventions to reduce the motivation that drives compulsive alcohol drinking...

Chronic pain is a disease that encompasses both sensory and emotional elements. Opioids are highly effective analgesics because they target both of these elements, by inhibiting pain pathways and alleviating negative affect (including depression) by engaging reward or hedonic pathways. Unfortunately, chronic opioid use is limited by the development of unwanted side effects, such as tolerance, hyperalgesia, and abuse liability. Thus, the challenge of providing effective pain treatment while minimizing these unwanted side effects is an ongoing issue with significant clinical and societal impact...