Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of both conditioned and unconditioned responses, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear.…

The loss of behavioral flexibility is common across a number of neuropsychiatric illnesses. This may be in part due to the loss of the ability to detect or use changes in action-outcome contingencies to guide behavior. There is growing evidence that the ventral hippocampus plays a critical role in the regulation of flexible behavior and…

In obsessive-compulsive disorder (OCD), functional behaviors such as checking that a door is locked become dysfunctional, maladaptive, and debilitating. However, it is currently unknown how aversive and appetitive motivations interact to produce functional and dysfunctional behavior in OCD. Here we show a double dissociation in the effects of…

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic…

Sign- and goal-tracking are differentially associated with drug abuse-related behavior. Recently, it has been hypothesized that sign- and goal-tracking behavior are mediated by different neurobehavioral valuation systems, including differential incentive salience attribution. Herein, we used different conditioned stimuli to preferentially elicit…

Active avoidance (AA) is an important paradigm for studying mechanisms of aversive instrumental learning, pathological anxiety, and active coping. Unfortunately, AA neurocircuits are poorly understood, partly because behavior is highly variable and reflects a competition between Pavlovian reactions and instrumental actions. Here we exploited the…

BDNF-induced signaling is essential for the development of the central nervous system and critical for plasticity in adults. Mature BDNF signals through TrkB, while its precursor proBDNF employs p75[superscript NTR], resulting in activation of signaling cascades with opposite effects on neuronal survival, growth cone decisions, and synaptic…