Search

The dynamic suppression of threat-related behavior as a function of environmental constraint is critical for survival in mammals, yet the neurobiological underpinnings remain largely unknown. In this issue of Neuron, Wang et al. 1 identified prefrontal dynorphin-expressing neurons as key elements for tracking threat-related behavioral states and regulating fear suppression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Translational research on post-traumatic stress disorder (PTSD) has produced limited improvements in clinical practice. Fear conditioning (FC) is one of the dominant animal models of PTSD. In fact, FC is used in many different ways to model PTSD. The variety of FC-based models is ill defined, creating confusion and conceptual vagueness, which in turn impedes translation into the clinic. This article takes a historical and conceptual approach to provide a comprehensive picture of current research and help reorient the research focus. This work historically reviews the variety of models that have emerged from the initial association of PTSD with FC, highlighting conceptual pitfalls that have limited the translation of animal research into clinical advances. We then provide some guidance on how future translational research could benefit from conceptual and technological improvements to translate basic findings in patients. This objective will require transdisciplinary approaches and should involve physicians, engineers, philosophers, and neuroscientists., Competing Interests: Declaration of interests B.A. received speaker’s honoraria and/or a travel allowance from Lundbeck, Janssen-Cilag, Sanofi, and Eli Lilly. He has served on the advisory board of Janssen-Cilag., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Survival critically depends on selecting appropriate defensive or exploratory behaviors and is strongly influenced by the surrounding environment. Contextual discrimination is a fundamental process that is thought to depend on the prefrontal cortex to integrate sensory information from the environment and regulate adaptive responses to threat during uncertainty. However, the precise prefrontal circuits necessary for discriminating a previously threatening context from a neutral context remain unknown. Using a combination of single-unit recordings and optogenetic manipulations, we identified a neuronal subpopulation in the dorsal medial prefrontal cortex (dmPFC) that projects to the lateral and ventrolateral periaqueductal gray (l/vlPAG) and is selectively activated during contextual fear discrimination. Moreover, optogenetic activation and inhibition of this neuronal population promoted contextual fear discrimination and generalization, respectively. Our results identify a subpopulation of dmPFC-l/vlPAG-projecting neurons that control switching between different emotional states during contextual discrimination., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Memories are acquired and encoded within large-scale neuronal networks spanning different brain areas. The anatomical and functional specificity of such long-range interactions and their role in learning is poorly understood. The amygdala and the medial prefrontal cortex (mPFC) are interconnected brain structures involved in the extinction of conditioned fear. Here, we show that a defined subpopulation of basal amygdala (BA) projection neurons targeting the prelimbic (PL) subdivision of mPFC is active during states of high fear, whereas BA neurons targeting the infralimbic (IL) subdivision are recruited, and exhibit cell-type-specific plasticity, during fear extinction. Pathway-specific optogenetic manipulations demonstrate that the activity balance between pathways is causally involved in fear extinction. Together, our findings demonstrate that, although intermingled locally, long-range connectivity defines distinct subpopulations of amygdala projection neurons and indicate that the formation of long-term extinction memories depends on the balance of activity between two defined amygdala-prefrontal pathways., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Classical fear conditioning is a powerful behavioral paradigm that is widely used to study the neuronal substrates of learning and memory. Previous studies have clearly identified the amygdala as a key brain structure for acquisition and storage of fear memory traces. Whereas the majority of this work has focused on principal cells and glutamatergic transmission and its plasticity, recent studies have started to shed light on the intricate roles of local inhibitory circuits. Here, we review current understanding and emerging concepts of how local inhibitory circuits in the amygdala control the acquisition, expression, and extinction of conditioned fear at different levels.

Functional compartmentalization of dendrites is thought to underlie afferent-specific integration of neural activity in laminar brain structures. Here we show that in the lateral nucleus of the amygdala (LA), an area lacking apparent laminar organization, thalamic and cortical afferents converge on the same dendrites, contacting neighboring but morphologically and functionally distinct spine types. Large spines contacted by thalamic afferents exhibited larger Ca(2+) transients during action potential backpropagation than did small spines contacted by cortical afferents. Accordingly, induction of Hebbian plasticity, dependent on postsynaptic spikes, was restricted to thalamic afferents. This synapse-specific effect involved activation of R-type voltage-dependent Ca(2+) channels preferentially located at thalamic inputs. These results indicate that afferent-specific mechanisms of postsynaptic, associative Hebbian plasticity in LA projection neurons depend on local, spine-specific morphological and molecular properties, rather than global differences between dendritic compartments.