McNally, G. P. | Search bioRxiv

bioRxiv2017

Brief optogenetic inhibition of rat lateral or ventrolateral periaqueductal gray augments the acquisition of Pavlovian fear conditioning.

The midbrain periaqueductal gray (PAG) coordinates the expression and topography of defensive behaviors to threat and also plays an important role in Pavlovian fear learning itself. Whereas the role of PAG in expression of defensive behavior is well understood, the relationship between activity of PAG neurons and fear learning, the exact timing of PAG contributions to learning during the conditioning trial, and the contributions of different PAG columns to fear learning are poorly understood. We assessed the effects of optogenetic inhibition of lateral (LPAG) and ventrolateral (VLPAG) PAG neurons on fear learning. Using adenoassociated viral vectors expressing halorhodopsin (eNpHR3.0), we show that brief optogenetic inhibition of LPAG or VLPAG during delivery of the shock unconditioned stimulus (US) augments acquisition of contextual or cued fear conditioning and we also show that this inhibition augments post-encounter defensive responses to a non-noxious threat. Taken together, these results show that LPAG and VLPAG serve a key role in regulation of Pavlovian fear learning at the time of US delivery. These findings provide strong support for existing models which state that LPAG and VLPAG contribute to a fear prediction error signal determining variations in the effectiveness of the aversive US in supporting learning.

neuroscience↗

bioRxiv2017

Basolateral amygdala glutamatergic neurons maintain aversive emotional salience

Basolateral amygdala (BLA) glutamatergic neurons serve a well-accepted role in fear conditioning and fear extinction. However, the specific learning processes related to their activity at different times during learning remain poorly understood. We addressed this using behavioral tasks isolating distinct aspects of fear learning in rats. We show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of aversive reinforcement or non-reinforcement causes reductions in the salience of conditioned stimuli, rendering these stimuli less able to be learned about and less able to control fear or safety behaviours. This salience reduction was stimulus-specific, long-lasting, and specific to aversive emotional states - precisely the goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition. They show that a primary function of BLA glutamatergic neurons is to maintain the salience of conditioned stimuli. This is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior.\n\nSignificance statementThe amygdala is essential for learning to fear and learning to reduce fear. However, the specific roles served by activity of different amygdala neurons at different times during learning is poorly understood. We used behavioral tasks isolating distinct aspects of learning in rats to show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of reinforcement or non-reinforcement disrupts maintenance of conditioned stimulus (CS) salience. This causes a stimulus-specific, long-lasting, and aversive emotion specific deficit in the ability of the CS to be learned about or control fear responses. These consequences are the precisely goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition.

neuroscience↗