Discrimination between sensory stimuli associated with safety and threat is crucial for behavioral decisions. Discriminative conditioning paradigms with two acoustic conditioned stimuli (one paired with shock [CS+], the other unpaired with shock [CS-]) have been widely used as an experimental model for fear learning. However, no attention has been…

Operant reward learning of feeding behavior in "Aplysia" increases the frequency and regularity of biting, as well as biases buccal motor patterns (BMPs) toward ingestion-like BMPs (iBMPs). The engram underlying this memory comprises cells that are part of a central pattern generating (CPG) circuit and includes increases in the intrinsic…

Threat conditioning is a common associative learning model with translational relevance. How threat-conditioned cues impact on formally unrelated instrumental behavior in humans is not well known. Such an effect is known as Pavlovian-to-instrumental transfer (PIT). While PIT with aversive primary Pavlovian reinforcers is established in nonhuman…

Long-term but not short-term memory and synaptic plasticity in many brain areas require neurotrophin signaling, transcription, and epigenetic mechanisms including DNA methylation. However, it has been difficult to relate these cellular mechanisms directly to behavior because of the immense complexity of the mammalian brain. To address that…

Multiple lines of evidence suggest that glucocorticoid hormones enhance memory consolidation of fearful events. However, most of these studies involve male individuals. Since anxiety, fear, and fear-associated disorders present differently in male and female subjects we investigated in mice whether male and female mice perform differently in a…

When discrete localizable stimuli are used during appetitive Pavlovian conditioning, "sign-tracking" and "goal-tracking" responses emerge. Sign-tracking is observed when conditioned responding is directed toward the CS, whereas goal-tracking manifests as responding directed to the site of expected reward delivery. These…

Anxiety disorders emerge early, and girls are significantly more likely to develop anxiety compared to boys. However, sex differences in fear during development are poorly understood. Therefore, we investigated juvenile male and female rats in the relapse behaviors following extinction of conditioned fear. In all experiments, 18-d-old rats first…

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned…

Development and sex differentiation impart an organizational influence on the neuroanatomy and behavior of mammalian species. Prior studies suggest that brain regions associated with fear motivated defensive behavior undergo a protracted and sex-dependent development. Outside of adult animals, evidence for developmental sex differences in…

Hippocampal ? (3-12 Hz) oscillations are implicated in learning and memory, but their functional role remains unclear. We studied the effect of the phase of local ? oscillation on hippocampal responses to a neutral conditioned stimulus (CS) and subsequent learning of classical trace eyeblink conditioning in adult rabbits. High-amplitude, regular…

Conventional wisdom dictates we must face our fears to conquer them. This idea is embodied in exposure-based treatments for anxiety disorders, where the intent of exposure is to reverse a history of avoidant behavior that is thought to fuel a patient's irrational fears. We tested in humans the relationship between fear and avoidance by combining…

There is growing interest in generalization of learned contextual fear, driven in part by the hypothesis that mood and anxiety disorders stem from impaired hippocampal mechanisms of fear generalization and discrimination. However, there has been relatively little investigation of the behavioral and procedural mechanisms that might control…

Single-cue delay eyeblink conditioning is presented as a prototypical example of automatic, nonsymbolic learning that is carried out by subcortical circuits. However, it has been difficult to assess the role of cognition in single-cue conditioning because participants become aware of the simple stimulus contingency so quickly. In this experiment…

Calcitonin gene-related peptide (CGRP) infusions into the bed nucleus of the stria terminalis (BNST) evoke increases in startle amplitude and increases in anxiety-like behavior in the plus maze. Conversely, intra-BNST infusions of the CGRP antagonist CGRP[subscript 8-37] block unconditioned startle increases produced by fox odor. Here we evaluate…

An issue of increasing theoretical and translational importance is to understand the conditions under which learned fear can be suppressed, or even eliminated. Basic research has pointed to extinction, in which an organism is exposed to a fearful stimulus (such as a context) in the absence of an expected aversive outcome (such as a shock). This…