State- and Circuit-Dependent Opponent Processing of Fear.

The presence of valence coding neurons in the basolateral amygdala (BLA) that form distinct projections to other brain regions implies functional opposition between aversion and reward during learning. However, evidence for opponent interactions in fear learning is sparse and may only be apparent under certain conditions. Here we test this possibility by studying the roles of the BLA→central amygdala (CeA) and BLA→nucleus accumbens (Acb) pathways in fear learning in male rats.

The Rescorla-Wagner model, prediction error, and fear learning.

The Rescorla-Wagner model remains one of the most important and influential theoretical accounts of the conditions under which Pavlovian learning occurs. Moreover, the experimental approaches that inspired the model continue to provide powerful behavioral tools to advance mechanistic understanding of how we and other animals learn to fear and learn to reduce fear. Here we consider key features of the Rescorla-Wagner model as applied to study of fear learning.

The activity of ventral tegmental area dopamine neurons during shock omission predicts safety learning.

We studied the role of dopamine [tyrosine hydroxylase (TH)] neurons in the rat ventral tegmental area (VTA) in safety learning. First, we used an AX +/BX-discrimination procedure to establish conditioned stimulus (CS) B as a learned safety signal that passed both summation and retardation tests of conditioned inhibition. Then, we combined this procedure with fiber photometry in TH-Cre rats to study the activity of VTA dopamine neurons during safety learning.

The Roles of Basolateral Amygdala Parvalbumin Neurons in Fear Learning.

The basolateral amygdala (BLA) is obligatory for fear learning. This learning is linked to BLA excitatory projection neurons whose activity is regulated by complex networks of inhibitory interneurons, dominated by parvalbumin (PV)-expressing GABAergic neurons. The roles of these GABAergic interneurons in learning to fear and learning not to fear, activity profiles of these interneurons across the course of fear learning, and whether or how these change across the course of learning all remain poorly understood.

Neural substrates of appetitive and aversive prediction error.

Prediction error, defined by the discrepancy between real and expected outcomes, lies at the core of associative learning. Behavioural investigations have provided evidence that prediction error up- and down-regulates associative relationships, and allocates attention to stimuli to enable learning. These behavioural advances have recently been followed by investigations into the neurobiological substrates of prediction error.

The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking.

The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking in male rats are assembled from activity across the VTA and the nucleus accumbens.

Pharmacogenetic excitation of dorsomedial prefrontal cortex restores fear prediction error.

Pavlovian conditioning involves encoding the predictive relationship between a conditioned stimulus (CS) and an unconditioned stimulus, so that synaptic plasticity and learning is instructed by prediction error. Here we used pharmacogenetic techniques to show a causal relation between activity of rat dorsomedial prefrontal cortex (dmPFC) neurons and fear prediction error. We expressed the excitatory hM3Dq designer receptor exclusively activated by a designer drug (DREADD) in dmPFC and isolated actions of prediction error by using an associative blocking design.