School of Psychology and.
Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, 2052 New South Wales, Australia.
J Neurosci. 2018 Mar 21;38(12):3001-3012. doi: 10.1523/JNEUROSCI.2460-17.2017. Epub 2017 Oct 27.
BLA 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 male rats. We show that brief optogenetic inhibition of BLA neurons around moments of aversive reinforcement or nonreinforcement 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 behaviors. This salience reduction was stimulus-specific, long-lasting, and specific to learning about, or responding to, the same aversive outcome, 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 the unconditioned stimulus-evoked activity of BLA neurons is to maintain the salience of conditioned stimuli that precede it. This maintenance of salience is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior. The 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 neurons around moments of reinforcement or nonreinforcement disrupts maintenance of conditioned stimulus salience. This causes a stimulus-specific and long-lasting deficit in the ability of the conditioned stimulus 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.
BLA 神经元在恐惧条件反射和恐惧消退中起着公认的作用。然而，它们在学习过程中的不同时间的活动所涉及的具体学习过程仍知之甚少。我们使用行为任务在雄性大鼠中分离出恐惧学习的不同方面来解决这个问题。我们表明，在令人不快的强化或非强化时刻周围，短暂的光遗传学抑制 BLA 神经元会导致条件刺激的显着性降低，从而使这些刺激更难以学习和控制恐惧或安全行为。这种显着性降低是刺激特异性的，持久的，并且专门针对学习或对相同的厌恶结果做出反应，这正是人类焦虑障碍的治疗干预的目标。我们的发现确定了一个被短暂 BLA 光遗传学抑制破坏的核心学习过程。它们表明，BLA 神经元的非条件刺激诱发活动的主要功能是维持其之前的条件刺激的显着性。这种显着性的维持是这些刺激获得并维持对恐惧和安全行为的控制的必要前提。杏仁核对于学习恐惧和学习减少恐惧至关重要。然而，在学习过程中的不同时间，不同杏仁核神经元的活动所起的具体作用仍知之甚少。我们使用行为任务在大鼠中分离出学习的不同方面，表明在强化或非强化时刻周围，短暂的 BLA 光遗传学抑制会破坏条件刺激显着性的维持。这会导致条件刺激被学习或控制恐惧反应的能力出现特定于刺激的、持久的缺陷。这些后果正是人类焦虑障碍的治疗干预的目标。我们的发现确定了一个被短暂 BLA 光遗传学抑制破坏的核心学习过程。
