Classical fear conditioning is an experimental model used to study how organisms learn to predict danger from previous experiences. In this model, a neutral sensory stimulus (conditioned stimulus, CS) acquires the ability to elicit fear responses after pairing with a noxious unconditioned stimulus (US). Early on, it was recognized that the amygdala is critical for this form of learning. However, identification of pathways that mediate the expression of conditioned responses by way of amygdala outputs and pathways that transmit CS information from sensory systems to the amygdala greatly increased interest in the intra-amygdaloid substrates of Pavlovian fear learning.
    Several factors account for this surge of interest. First, the simplicity of this experimental paradigm facilitates the study of underlying mechanisms in animal models. Second, findings from animal studies have been confirmed in humans with fMRI imaging techniques, increasing the relevance of the animal model. Third, it is becoming increasingly apparent that the mechanisms underlying Pavlovian fear conditioning have much in common with human anxiety disorders. Thus, understanding the acquisition and extinction of conditioned fear might help us find ways to treat these disorders.
    Currenty, our research focuses on (1) the intra-amygdaloid pathways involved in the acquisition of conditioned fear responses and (2) their modulation by the medial prefrontal cortex during extinction. (click on the image to enlarge)

Recent publications on this theme:
Likhtik E, Popa D, Apergis-Schoute A, Fidacaro GA, Paré D (2008) Amygdala intercalated neurons are required for expression of fear extinction. Nature, 454:642-645.

Samson R, Paré D (2005) Activity-dependent synaptic plasticity in the central nucleus of the amygdala. J Neurosci, 25(7):1847-1855.

Paré D, Quirk GJ, LeDoux JE (2004) New vistas on amygdala networks in conditioned fear. J Neurophysiol, 92: 1-9.

Quirk GJ, Likhtik E, Pelletier JG, Paré D (2003) Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci, 23: 8800-8807.

Emotionally charged events are generally better remembered than neutral ones. The available data suggests that the amygdala is responsible for this modulation of memory consolidation by emotions. In short, neuromodulators released in emotionally arousing conditions would alter the activity of basolateral amygdala (BLA) neurons in the hours after the learning episode.In turn, these changes would facilitate synaptic plasticity elsewhere in the brain. This view emerged from behavioral analyses of the effects of intra-amygdaloid drug injections; however, we have no direct evidence that these events take place. Moreover, we do not know how transient increases in neuromodulator levels could exert a sustained effect on BLA neurons. Considering the devastating psychological consequences of extreme stress, understanding how the amygdala modulates memory emerges as an issue of fundamental importance. Thus, we are investigating this issue using a combination of behavioral experiments, multisite in vivo extracellular recordings and in vitro whole cell (standard and perforated patch) recordings in amygdala slices. (click on the image to enlarge)

Recent publications on this theme:
Popescu A, Popa D, Paré D (2009) Coherent gamma oscillations couple the amygdala and striatum during learning. Nature Neuroscience, 12:801-807.

Popescu AT*, Saghyan AA*, Paré D (2007) NMDA-dependent facilitation of corticostriatal plasticity by the amygdala. Proc Natl Acad Sci USA, 104:341-346.

Duvarci S, Paré D (2007) Glucocorticoids enhance the excitability of principal basolateral amygdala neurons. J Neurosci 27:4482-4491.

Pelletier J-G*, Likhtik E,* Filali M, Paré D (2005) Lasting increases in basolateral amygdala activity after emotional arousal: implications for facilitated consolidation of emotional memories. Learning and Memory,12: 96-102.

Paré D (2003) Role of the basolateral amygdala in memory consolidation. Prog Neurobiol, 70: 409-420.

The rhinal cortices play a critical role in high-order perceptual/mnemonic functions and constitute the main route for impulse traffic to and from the hippocampus. However, there is a discrepancy between anatomical and physiological data about this network. Tracing studies indicate that the perirhinal cortex forms strong reciprocal connections with the neo- and entorhinal cortex. In contrast, physiological studies indicate that perirhinal transmission of neocortical and entorhinal inputs occurs with an extremely low probability. Currently, our work aims (1) to shed light on the inhibitory mechanisms that limit impulse traffic through the rhinal cortices and (2) to identify the afferents that allow the rhinal cortices to overcome this inhibition, focusing on inputs from the medial prefrontal cortex and amygdala. (click on the image to enlarge)

Recent publications on this theme:
*Paz R, *Bauer EP, Paré D (2007) Learning-related facilitation of rhinal interactions by medial prefrontal inputs. J Neurosci, 27:9369-79.

*Paz R, *Pelletier JG, Bauer EP, Paré D (2006) Emotional enhancement of memory via amygdala-driven facilitation of rhinal interactions. Nature Neuroscience,9: 1321-1329.

*Pelletier JG, *Apergis J, Paré D (2004) Low probability transmission of neocortical and entorhinal impulses through the perirhinal cortex. J Neurophysiol, 91:2079-2089.

De Curtis M, Paré D (2004) The rhinal cortices: a wall of inhibition between the neocortex and hippocampus. Prog Neurobiol, 74: 101-110.

This theme is closely related to (1) our interest in understanding the modulation of memory consolidation by the amygdala, and (2) the ability of the amygdala to form a trace of some stimulus contingencies. With respect to the first issue, our work aims to identify how amygdala axons promote synaptic plasticity in target structures. Our working hypothesis is that there is a higher NMDA to AMPA ration at amygdala synapses and that this property would promote heterosynaptic plasticity of other inputs to the same cells. With respect to the second theme, we are currently examining the ability of inputs to various amygdala cell types to undergo activity-dependent plasticity. (click on the image to enlarge)

Recent publications on this theme:
Samson R, Paré D (2005) Activity-dependent synaptic plasticity in the central nucleus of the amygdala. J. Neurosci., 25: 1847-1855.

Royer S, Paré D (2003) Conservation of total synaptic weights via inverse homo- vs. heterosynaptic LTD and LTP. Nature 422: 518-522.

The amygdala is a nucleated structure of the temporal lobe critical for the expression and learning of fear responses. As a result, it is widely believed that disturbances in amygdala physiology underlie human anxiety disorders. However, the inner workings of the amygdala remain obscure, in part because we do not understand its intrinsic network. This is why we are studying the intrinsic circuit of the amygdala, using in vitro and in vivo electrophysiological methods as well as single-cell labeling and immunohistochemistry at the light and electron microscopic level. As a first step, we focus on the lateral amygdaloid nucleus (LA) because it is the main input station of the amygdala for sensory afferents. (click on the image to enlarge)

Recent publications on this theme:
Samson R, Paré D (2006) A spatially structured network of inhibitory and excitatory connections directs impulse traffic within the lateral amygdala. Neuroscience 141(3):1599-609.

Samson R, Dumont EC, Paré D (2003) Feedback inhibition defines transverse processing modules in the lateral amygdala. J. Neurosci. 23:1966-1973.

Paré D, Royer S, Smith Y, Lang EJ (2003) Contextual inhibitory gating of impulse traffic in the intra-amygdaloid network. Annals of the New York Academy of Science 985: 78-91.