Molecular diversity and functional dynamics in the central amygdala.

The central amygdala (CeA) is crucial in integrating sensory and associative information to mediate adaptive responses to emotional stimuli. Recent advances in genetic techniques like optogenetics and chemogenetics have deepened our understanding of distinct neuronal populations within the CeA, particularly those involved in fear learning and memory consolidation. However, challenges remain due to overlapping genetic markers complicating neuron identification. Furthermore, a comprehensive understanding of molecularly defined cell types and their projection patterns, which are essential for elucidating functional roles, is still developing. Recent advancements in transcriptomics are starting to bridge these gaps, offering new insights into the functional dynamics of CeA neurons. In this review, we provide an overview of the expanding genetic markers for amygdala research, encompassing recent developments and current trends. We also discuss how novel transcriptomic approaches are redefining cell types in the CeA and setting the stage for comprehensive functional studies.

Functional organization of the midbrain periaqueductal gray for regulating aversive memory formation.

Innately aversive experiences produce rapid defensive responses and powerful emotional memories. The midbrain periaqueductal gray (PAG) drives defensive behaviors through projections to brainstem motor control centers, but the PAG has also been implicated in aversive learning, receives information from aversive-signaling sensory systems and sends ascending projections to the thalamus as well as other forebrain structures which could control learning and memory. Here we sought to identify PAG subregions and cell types which instruct memory formation in response to aversive events. We found that optogenetic inhibition of neurons in the dorsolateral subregion of the PAG (dlPAG), but not the ventrolateral PAG (vlPAG), during an aversive event reduced memory formation. Furthermore, inhibition of a specific population of thalamus projecting dlPAG neurons projecting to the anterior paraventricular thalamus (aPVT) reduced aversive learning, but had no effect on the expression of previously learned defensive behaviors. By contrast, inactivation of dlPAG neurons which project to the posterior PVT (pPVT) or centromedial intralaminar thalamic nucleus (CM) had no effect on learning. These results reveal specific subregions and cell types within PAG responsible for its learning related functions.

Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders.

Aversive experiences activate dedicated neural instructive pathways which trigger memory formation and change behavior. The strength of these aversive memories and the degree to which they alter behavior is proportional to the intensity of the aversive experience. Dysregulation of aversive learning circuits can lead to psychiatric pathology. Here we review recent findings elucidating aversive instructive signaling circuits for fear conditioning. We then examine how chronic pain as well as stress and anxiety disrupt these circuits and the implications this has for understanding and treating psychiatric disease. Together this review synthesizes current work on aversive instructive signaling circuits in health and disease and suggests a novel circuit based framework for understanding pain and anxiety syndromes.

A feedback neural circuit for calibrating aversive memory strength.

Aversive experiences powerfully regulate memory formation, and memory strength is proportional to the intensity of these experiences. Inhibition of the neural circuits that convey aversive signals when they are predicted by other sensory stimuli is hypothesized to set associative memory strength. However, the neural circuit mechanisms that produce this predictive inhibition to regulate memory formation are unknown. Here we show that predictive sensory cues recruit a descending feedback circuit from the central amygdala that activates a specific population of midbrain periaqueductal gray pain-modulatory neurons to control aversive memory strength. Optogenetic inhibition of this pathway disinhibited predicted aversive responses in lateral amygdala neurons, which store fear memories, resulting in the resetting of fear learning levels. These results reveal a control mechanism for calibrating learning signals to adaptively regulate the strength of behavioral learning. Dysregulation of this circuit could contribute to psychiatric disorders associated with heightened fear responsiveness.