Joseph E. LeDoux.

In an interview with Neuron, Joseph LeDoux outlines his early work on consciousness in split-brain patients, his transition into studying emotional behavior in rodents, and his continued exploration of consciousness in books and other writings. He describes how his research fused with his interest in music, which he pursued though his band, The Amygdaloids, and their unique genre, "heavy mental."

Distributed neural representations of conditioned threat in the human brain.

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established.

Consciousness, the affectome, and human life.

I have been working on interactions between conscious and non-conscious processes since the late 1970s. In this commentary, I offer a perspective on conscious/non-conscious interactions that might a useful adjunct to the Human Affectome Project as it evolves.

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept.

A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research.

A generative adversarial model of intrusive imagery in the human brain.

The mechanisms underlying the subjective experiences of mental disorders remain poorly understood. This is partly due to long-standing over-emphasis on behavioral and physiological symptoms and a de-emphasis of the patient's subjective experiences when searching for treatments. Here, we provide a new perspective on the subjective experience of mental disorders based on findings in neuroscience and artificial intelligence (AI).

Human threat learning is associated with gut microbiota composition.

The ability to learn about threat and safety is critical for survival. Studies in rodent models have shown that the gut microbiota can modulate such behaviors. In humans, evidence showing an association with threat or extinction learning is lacking.

The tricky business of defining brain functions.

Neuroscience has a long history of investigating the neural correlates of brain functions. One example is fear, which has been studied intensely in a variety of species. In parallel, unease about definitions of brain functions has existed for over 100 years.

The day I told Karim Nader, "Don't do the study".

Karim Nader changed the course of memory research by reviving interest in the mostly forgotten topic of post-retrieval manipulations of memory. In this paper I summarize the events leading up to his ground-breaking study in my lab on so-called memory reconsolidation, and the effects of that study on the field.

Temporally and anatomically specific contributions of the human amygdala to threat and safety learning.

Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses.

Putting the "mental" back in "mental disorders": a perspective from research on fear and anxiety.

Mental health problems often involve clusters of symptoms that include subjective (conscious) experiences as well as behavioral and/or physiological responses. Because the bodily responses are readily measured objectively, these have come to be emphasized when developing treatments and assessing their effectiveness. On the other hand, the subjective experience of the patient reported during a clinical interview is often viewed as a weak correlate of psychopathology.

As soon as there was life, there was danger: the deep history of survival behaviours and the shallower history of consciousness.

It is often said that fear is a universal innate emotion that we humans have inherited from our mammalian ancestors by virtue of having inherited conserved features of their nervous systems. Contrary to this common sense-based scientific point of view, I have argued that what we have inherited from our mammalian ancestors, and they from their distal vertebrate ancestors, and they from their chordate ancestors, and so forth, is not a fear circuit. It is, instead, a defensive survival circuit that detects threats, and in response, initiates defensive survival behaviours and supporting physiological adjustments.

Conditional Control of Instrumental Avoidance by Context Following Extinction.

Using rodents, three training arrangements (i.e., ABB vs.

Observation of others' threat reactions recovers memories previously shaped by firsthand experiences.

Information about dangers can spread effectively by observation of others' threat responses. Yet, it is unclear if such observational threat information interacts with associative memories that are shaped by the individual's direct, firsthand experiences. Here, we show in humans and rats that the mere observation of a conspecific's threat reactions reinstates previously learned and extinguished threat responses in the observer.

What emotions might be like in other animals.

In this My word, Joseph LeDoux explores what the emotional lives of other mammals might be like. He proposes that better understanding of the brain mechanisms of emotional consciousness in humans might shed light on the kinds of conscious capacities that might be possible in non-human primates and non-primate mammals, given the kinds of brains they possess.

The rise of affectivism.

Research over the past decades has demonstrated the explanatory power of emotions, feelings, motivations, moods, and other affective processes when trying to understand and predict how we think and behave. In this consensus article, we ask: has the increasingly recognized impact of affective phenomena ushered in a new era, the era of affectivism?

The bed nucleus of the stria terminalis and functionally linked neurocircuitry modulate emotion processing and HPA axis dysfunction in posttraumatic stress disorder.

Background: The bed nucleus of the stria terminalis (BNST) plays an important role in rodent posttraumatic stress disorder (PTSD), but evidence to support its relevance to human PTSD is limited. We sought to understand the role of the BNST in human PTSD via fMRI, behavioral, and physiological measurements.

Methods: 29 patients with PTSD (childhood sexual abuse) and 23 healthy controls (HC) underwent BOLD imaging with an emotional word paradigm.

Motivational factors underlying aversive Pavlovian-instrumental transfer.

While interest in active avoidance has recently been resurgent, many concerns relating to the nature of this form of learning remain unresolved. By separating stimulus and response acquisition, aversive Pavlovian-instrumental transfer can be used to measure the effect of avoidance learning on threat processing with more control than typical avoidance procedures. However, the motivational substrates that contribute to the aversive transfer effect have not been thoroughly examined.

Seeing consciousness through the lens of memory.

In this My Word, Joseph LeDoux and Hakwan Lau argue that everyday human conscious experiences cannot be understood separately from memory. The authors build on a tripartite model of memory as a way of fractionating consciousness into components that account for wide ranging experiences, from the simplest sensory experience of the color of an apple to a full-blown feeling of fear or other emotions.

Thoughtful feelings.

In this My Word, Joseph LeDoux describes how his four-decade career exploring how non-conscious processes involving the amygdala detect and respond to danger has contributed to the 'amygdala fear center' meme, a view he does not endorse. The conscious experience of fear, he tells us here, is not wired into the amygdala, but is instead a cognitively assembled understanding that you are in harm's way based on non-conscious memories, schemas, and mental models.

A little history goes a long way toward understanding why we study consciousness the way we do today.

Consciousness is currently a thriving area of research in psychology and neuroscience. While this is often attributed to events that took place in the early 1990s, consciousness studies today are a continuation of research that started in the late 19th century and that continued throughout the 20th century. From the beginning, the effort built on studies of animals to reveal basic principles of brain organization and function, and of human patients to gain clues about consciousness itself.

How does the non-conscious become conscious?

In this My Word, Joseph LeDoux describes how his work as a graduate student got him interested in human consciousness. Although he has not studied this topic since 1970s, he never stopped thinking and writing about it during his four-decade career exploring how non-conscious processes involving the amygdala detect and respond to danger. Here, he tells us what is on his mind about consciousness these days.

Cell-type-specific drug-inducible protein synthesis inhibition demonstrates that memory consolidation requires rapid neuronal translation.

New protein synthesis is known to be required for the consolidation of memories, yet existing methods of blocking translation lack spatiotemporal precision and cell-type specificity, preventing investigation of cell-specific contributions of protein synthesis. Here we developed a combined knock-in mouse and chemogenetic approach for cell-type-specific drug-inducible protein synthesis inhibition that enables rapid and reversible phosphorylation of eukaryotic initiation factor 2α, leading to inhibition of general translation by 50% in vivo. We use cell-type-specific drug-inducible protein synthesis inhibition to show that targeted protein synthesis inhibition pan-neuronally and in excitatory neurons in the lateral amygdala (LA) impaired long-term memory.

Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala.

Local translation can support memory consolidation by supplying new proteins to synapses undergoing plasticity. Translation in adult forebrain dendrites is an established mechanism of synaptic plasticity and is regulated by learning, yet there is no evidence for learning-regulated protein synthesis in adult forebrain axons, which have traditionally been believed to be incapable of translation. Here, we show that axons in the adult rat amygdala contain translation machinery, and use translating ribosome affinity purification (TRAP) with RNASeq to identify mRNAs in cortical axons projecting to the amygdala, over 1200 of which were regulated during consolidation of associative memory.