Joseph E. LeDoux

Memory and Emotion

My lab's research is aimed at understanding the biological mechanisms of emotional memory. We are particularly interested in how the brain learns and stores information about danger. Using classical fear conditioning as way of inducing emotional memories in rats, we have mapped the neural pathways by which sensory stimuli enter and flow through the brain in the process of fear learning. This work implicated specific circuits in within the amygdala as essential for the formation of memories of the fear conditioning experience. It is now clear that the same brain system underlies fear learning in and humans. The detailed mechanisms of fear, which can only be uncovered through animal studies, are thus applicable to understanding fear processing in the human brain.

With the neural system mediating fear learning now understood in considerable detail, we are pursuing the cellular and molecular mechanisms involved. This is being done by performing studies in which we compare the effects of pharmacological manipulations of the brain on fear learning in behaving animals and on long-term potentiation in vitro. Through such studies the neural plasticity underlying fear conditioning has been shown to involve elevation of calcium in amygdala cells through NMDA receptors and L-type voltage gated calcium channels. The elevated calcium activates protein kinases, which initiate gene expression and protein synthesis, leading to the consolidation of the memory, and its reconsolidation after retrieval.

Some of the techniques we use to explore emotional memory in the brain include brain lesions, neuroanatomical tract tracing at the light and electron microscopic level, pharmacological and viral manipulation of brain chemistry, single unit and field recordings of neural activity in awake and anesthetized animals, whole cell recordings in in vitro brain slices, and fMRI in healthy human volunteers and in patients with fear/anxiety disorders.

Conceptual issues being explored include the following. Is the same basic system that has been uncovered for the conditioning of reflexive responses also apply to voluntary behavioral responses in dangerous situations or do other networks become involved? How does the brain regulate fear, as in extinction or other processes? Are other emotions mediated by similar or different circuits? What are the mechanisms through which conscious emotional feelings, as opposed to behavioral or autonomic responses, come about?

E-mail: ledoux@cns.nyu.edu

Links:
LeDoux Lab Home Page
Center for the Neuroscience of Fear and Anxiety

Representative Publications

LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci. 23, 155-184.

Nader K, Schafe GE, LeDoux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722-726.

LeDoux JE, Gorman JM (2001) A call to action: Overcoming anxiety through active coping. Am J Psychiatry 158: 1953-1955.

LeDoux JE (2002) Emotion, Memory, and the Brain. Sci Am 12:62-71.

Rodrigues SM, Schafe GE, LeDoux JE (2004) Molecular mechanisms underlying emotional learning and memory in the lateral amygdala. Neuron 44:75-91.

Rumpel S, LeDoux J, Zador A, Malinow R (2005) Postsynaptic receptor trafficking underlying a form of associative learning. Science 308:83-88.

Doyere V, Debiec J, Monfils MH, Schafe GE, LeDoux JE (2007) Synapse-specific reconsolidation of distinct fear memories in the lateral amygdala. Nat Neurosci 10:414-416.

Burghardt NS, Bush DE, McEwen BS, LeDoux JE (2007) Acute Selective Serotonin Reuptake Inhibitors Increase Conditioned Fear Expression: Blockade With a 5-HT(2C) Receptor Antagonist. Biol Psychiatry 62:1111-1118.

Hu H, Real E, Takamiya K, Kang MG, LeDoux J, Huganir RL, Malinow R (2007) Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking. Cell 131:160-173.

Sigurdsson T, Doyere V, Cain CK, LeDoux JE (2007) Long-term potentiation in the amygdala: A cellular mechanism of fear learning and memory. Neuropharmacology 52:215-227.

LeDoux J (2007) The amygdala. Curr Biol 17:R868-874.

Delgado MR, Nearing KI, LeDoux JE, Phelps EA (2008) Neural circuitry underlying the regulation of conditioned fear and its relation to extinction. Neuron 59:829-838.

Schafe GE, LeDoux JE (2008) Neural and molecular mechanisms of fear memory. In: Learning & Memory: A comprehensive reference: Molecular mechanisms (Sweatt JD, ed): Academic Press.

LeDoux JE (in press) Emotional Coloration of Consciousness: How Feelings Come About. In: Frontiers of Consciousness (Weiskrantz LW, Davies M, eds). Oxford: Oxford University Press.

Book:

LeDoux, J.E. (1996) The Emotional Brain. New York, Simon and Schuster.

LeDoux J.E. (2002) Synaptic Self: How Our Brains Become Who We Are. New York, Viking.

Additional publications (PubMed)