Neurocentre Magendie

Julien COURTIN




11 publication(s) depuis Septembre 2011:


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21/07/2016 | Nature   IF 38.1
Prefrontal neuronal assemblies temporally control fear behaviour.
Dejean C, Courtin J, Karalis N, Chaudun F, Wurtz H, Bienvenu TC, Herry C

Abstract:
Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses.




15/02/2016 | Nat Neurosci   IF 16.7
4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior.
Karalis N, Dejean C, Chaudun F, Khoder S, Rozeske RR, Wurtz H, Bagur S, Benchenane K, Sirota A, Courtin J, Herry C

Abstract:
Fear expression relies on the coordinated activity of prefrontal and amygdala circuits, yet the mechanisms allowing long-range network synchronization during fear remain unknown. Using a combination of extracellular recordings, pharmacological and optogenetic manipulations, we found that freezing, a behavioral expression of fear, temporally coincided with the development of sustained, internally generated 4-Hz oscillations in prefrontal-amygdala circuits. 4-Hz oscillations predict freezing onset and offset and synchronize prefrontal-amygdala circuits. Optogenetic induction of prefrontal 4-Hz oscillations coordinates prefrontal-amygdala activity and elicits fear behavior. These results unravel a sustained oscillatory mechanism mediating prefrontal-amygdala coupling during fear behavior.




01/09/2015 | Biol Psychiatry   IF 8.9
Neuronal Circuits for Fear Expression and Recovery: Recent Advances and Potential Therapeutic Strategies.
Dejean C, Courtin J, Rozeske RR, Bonnet MC, Dousset V, Michelet T, Herry C

Abstract:
Recent technological developments, such as single unit recordings coupled to optogenetic approaches, have provided unprecedented knowledge about the precise neuronal circuits contributing to the expression and recovery of conditioned fear behavior. These data have provided an understanding of the contributions of distinct brain regions such as the amygdala, prefrontal cortex, hippocampus, and periaqueductal gray matter to the control of conditioned fear behavior. Notably, the precise manipulation and identification of specific cell types by optogenetic techniques have provided novel avenues to establish causal links between changes in neuronal activity that develop in dedicated neuronal structures and the short and long-lasting expression of conditioned fear memories. In this review, we provide an update on the key neuronal circuits and cell types mediating conditioned fear expression and recovery and how these new discoveries might refine therapeutic approaches for psychiatric conditions such as anxiety disorders and posttraumatic stress disorder.




16/06/2015 | Neuroscience   IF 3.2
Preventing long-lasting fear recovery using bilateral alternating sensory stimulation: A translational study.
Wurtz H, El-Khoury-Malhame M, Wilhelm FH, Michael T, Beetz EM, Roques J, Reynaud E, Courtin J, Khalfa S, Herry C

Abstract:
Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery.




11/2014 | Med Sci (Paris)
[Prefrontal parvalbumin-expressing interneurons control fear behavior].
Courtin J, Dejean C, Herry C

Abstract:





17/03/2014 | Neuropsychopharmacology   IF 7.8
Frequency of Cocaine Self-Administration Influences Drug Seeking in the Rat: Optogenetic Evidence for a Role of the Prelimbic Cortex.
Martin-Garcia E, Courtin J, Renault P, Fiancette JF, Wurtz H, Simonnet A, Levet F, Herry C, Deroche-Gamonet V

Abstract:
High-frequency intake and high drug-induced seeking are associated with cocaine addiction in both human and animals. However, their relationships and neurobiological underpinnings remain hypothetical. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and nucleus accumbens (NAc) have been shown to have a role in cocaine seeking. However, their involvement in regulating high-frequency intake and high cocaine-induced seeking is unclear. We manipulated frequency of cocaine self-administration and investigated whether it influenced cocaine seeking. The contribution of the aforementioned structures was evaluated using changes in expression of the immediate early gene c-Fos and targeted optogenetic manipulations. Rats that self-administered at High frequency (short inter-infusion intervals allowed by short time-out) showed higher cocaine-induced seeking than low frequency rats (long inter-infusions intervals imposed by long time-out), as measured with cocaine-induced reinstatement. c-Fos was enhanced in High frequency rats in the prelimbic (PL) and infralimbic (IL) areas of the mPFC, the BLA, and the NAc core and shell. Correlational analysis of c-Fos revealed that the PL was a critical node strongly correlated with both the IL and NAc core in High frequency rats. Targeted optogenetic inactivation of the PL decreased cocaine-induced reinstatement, but increased cocaine self-administration, in High frequency rats. In contrast, optogenetic activation of the PL had no effect on Low frequency rats. Thus, high-frequency intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory or inhibitory effect, depending on operant contingencies. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake.Neuropsychopharmacology advance online publication, 16 April 2014; doi:10.1038/npp.2014.66.




02/01/2014 | Nature   IF 38.1
Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression.
Courtin J, Chaudun F, Rozeske RR, Karalis N, Gonzalez-Campo C, Wurtz H, Abdi A, Baufreton J, Bienvenu TC, Herry C

Abstract:
Synchronization of spiking activity in neuronal networks is a fundamental process that enables the precise transmission of information to drive behavioural responses. In cortical areas, synchronization of principal-neuron spiking activity is an effective mechanism for information coding that is regulated by GABA (gamma-aminobutyric acid)-ergic interneurons through the generation of neuronal oscillations. Although neuronal synchrony has been demonstrated to be crucial for sensory, motor and cognitive processing, it has not been investigated at the level of defined circuits involved in the control of emotional behaviour. Converging evidence indicates that fear behaviour is regulated by the dorsomedial prefrontal cortex (dmPFC). This control over fear behaviour relies on the activation of specific prefrontal projections to the basolateral complex of the amygdala (BLA), a structure that encodes associative fear memories. However, it remains to be established how the precise temporal control of fear behaviour is achieved at the level of prefrontal circuits. Here we use single-unit recordings and optogenetic manipulations in behaving mice to show that fear expression is causally related to the phasic inhibition of prefrontal parvalbumin interneurons (PVINs). Inhibition of PVIN activity disinhibits prefrontal projection neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. Our results identify two complementary neuronal mechanisms mediated by PVINs that precisely coordinate and enhance the neuronal activity of prefrontal projection neurons to drive fear expression.




30/09/2013 | Neurobiol Learn Mem   IF 3.4
Persistence of amygdala gamma oscillations during extinction learning predicts spontaneous fear recovery.
Courtin J, Karalis N, Gonzalez-Campo C, Wurtz H, Herry C

Abstract:
Extinction of auditory fear conditioning induces a temporary inhibition of conditioned fear responses that can spontaneously reappear with the passage of time. Several lines of evidence indicate that extinction learning relies on the recruitment of specific neuronal populations within the basolateral amygdala. In contrast, post-extinction spontaneous fear recovery is thought to result from deficits in the consolidation of extinction memory within prefrontal neuronal circuits. Interestingly, recent data indicates that the strength of gamma oscillations in the basolateral amygdala during auditory fear conditioning correlates with retrieval of conditioned fear responses. In the present manuscript we evaluated the hypothesis that post-extinction spontaneous fear recovery might depend on the maintenance of gamma oscillations within the basolateral amygdala by using single unit and local field potential recordings in behaving mice. Our results indicate that gamma oscillations in the basolateral amygdala were enhanced following fear conditioning, whereas during extinction learning gamma profiles were more heterogeneous despite similar extinction learning rates. Remarkably, variations in the strength of gamma power within the basolateral amygdala between early and late stages of extinction linearly predicted the level of post-extinction spontaneous fear recovery. These data suggest that maintenance of gamma oscillations in the basolateral amygdala during extinction learning is a strong predictive factor of long term spontaneous fear recovery.




14/06/2013 | Neuroscience   IF 3.2
Medial prefrontal cortex neuronal circuits in fear behavior
Courtin J, Bienvenu T, Einarsson EO, Herry C

Abstract:
he medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies have established a canonical view of mPFC functions during fear behavior with dorsal regions selectively involved in the expression of fear behavior and ventral regions linked to the inhibition of fear behavior. Although numerous reports support this view, recent data have refined this model and suggested that dorsal prefrontal regions might also play an important role in the encoding of fear behavior itself. The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior.




15/12/2011 | Nature   IF 38.1
A disinhibitory microcircuit for associative fear learning in the auditory cortex.
Letzkus JJ, Wolff SB, Meyer EM, Tovote P, Courtin J, Herry C, Luthi A

Abstract:
Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local networks contribute to the process of learning. Here we show that acquisition of associative fear memories depends on the recruitment of a disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn generating inhibition of layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or optogenetic block of pyramidal neuron disinhibition abolishes fear learning. Together, these data demonstrate that stimulus convergence in the auditory cortex is necessary for associative fear learning to complex tones, define the circuit elements mediating this convergence and suggest that layer-1-mediated disinhibition is an important mechanism underlying learning and information processing in neocortical circuits.