Cyril Herry

French Institute of Health and Medical Research | Inserm

Imbalance between excitation and inhibition in the cerebral cortex is one of the main theories in neuropsychiatric disorder pathophysiology. Cortical inhibition is finely regulated by a variety of highly specialized GABAergic interneuron types, which are thought to organize neural network activities. Among interneurons, axo-axonic cells are unique...

Consolidation of recent memory depends on hippocampal activities during resting periods that immediately follows the memory encoding. There, Slow Save Sleep phases appear as privileged periods for memory consolidation as hosting the ripple activities, which are fast oscillations generated within the hippocampus whose inactivation leads to memory im...

The value of rewards and punishments – namely, how good or bad they are perceived – guides approach or avoidance behaviors. Valence refers to the negative or positive “sign” of the state elicited by an event, whereas salience refers to the amount of attention an event attracts, disregarding its valence. While identifying these signals conveys criti...

In mammals, the ability to optimize and select behavioral strategies is a cardinal and conserved psychophysiological feature for maximizing the chances of survival. However, the neural circuits and underlying mechanisms regulating this flexible feature remain yet unsolved. Here, we demonstrate that such optimization relies on dopamine D2 receptors...

Fear acquisition is a survival strategy enabling the prediction of potential threat on the basis of reliable environmental cues identified through associative learning. In this study we investigated the role of dorsomedial prefrontal cortex (dmPFC) -ventral tegmental area (VTA) coordination in fear acquisition. Despite the implication of a VTA-dmPF...

Background- Advances in in vivo fluorescent imaging have exploded with the recent developments of genetically encoded calcium indicators (GECIs) and fluorescent biosensors. Their use with a bulk imaging technique such as fiber photometry (FP) can be highly beneficial in identifying neuronal signatures in behavioral neuroscience experiments. Popular...

Upon threatening situations, animals exhibit a broad range of behavioral and autonomic responses necessary for survival. Under such conditions, a crucial adaptive response is the inhibition of pain responses that would otherwise interfere with behavioral defensive responses. Whereas the structures and mechanisms involved in fear and pain behavior a...

Descending control from the brain to the spinal cord shapes our pain experience, ranging from powerful analgesia to extreme sensitivity. Increasing evidence from both preclinical and clinical studies points to an imbalance toward descending facilitation as a substrate of pathological pain, but the underlying mechanisms remain unknown. We used an op...

Our understanding of the neuronal circuits and mechanisms of defensive systems has been primarily dominated by studies focusing on the contribution of individual cells in the processing of threat-predictive cues, defensive responses, the extinction of such responses and the contextual modulation of threat-related behavior. These studies have been k...

14 15 In mammals, threat-related behavior is typically induced by a noxious physical stressor and 16 is associated with a broad range of behavioral responses such as freezing and avoidance. 17 These behavioral responses are associated with the regulation of pain responses allowing 18 individuals to cope with noxious stimuli. Whereas the structures...

Survival critically depends on the memorization of stimuli recurrently predicting pleasant or aversive experiences. Memory strengthening by additional learning is a critical process allowing the long-term stabilization of learned aversive experience. However, the underlying neuronal circuits and mechanisms are still largely unknown. Using a combina...

The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated the role of dentate granule neurons (DGNs) born during adolescence in spatial memory and compared them with those generated earlier in lif...

Coping with threatening situations requires both identifying stimuli that predict danger and selecting adaptive behavioural responses to survive1. The dorsomedial prefrontal cortex (dmPFC) is a critical structure that is involved in the regulation of threat-related behaviour2–4. However, it is unclear how threat-predicting stimuli and defensive beh...

Fear extinction is an adaptive process whereby defensive responses are attenuated following repeated experience of prior fear-related stimuli without harm. The formation of extinction memories involves interactions between various corticolimbic structures, resulting in reduced central amygdala (CEA) output. Recent studies show, however, the CEA is...

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 tu...

Brain–body interactions are thought to be essential in emotions but their physiological basis remains poorly understood. In mice, regular 4 Hz breathing appears during freezing after cue-fear conditioning. Here we show that the olfactory bulb (OB) transmits this rhythm to the dorsomedial prefrontal cortex (dmPFC) where it organizes neural activity....

The ability to efficiently switch from one defensive strategy to another maximizes an animals chance of survival. Here, we demonstrate that the selection of active defensive behaviors requires the coordinated activation of dopamine D2 receptor (D2R) signaling within the central extended amygdala (EA) comprising the nucleus accumbens, the oval bed n...

Does the body play an active role in emotions? Since the original James/Cannon controversy this debate has mainly been fueled by introspective accounts of human experience. Here, we use the animal model to demonstrate a physiological mechanism for bodily feedback and its causal role in the stabilization of emotional states. We report that during fe...

Les émotions négatives sont surexprimées dans les pathologies thymiques et anxieuses. Une meilleure compréhension des mécanismes physiopathologiques à l’origine de l’expression des émotions négatives pourrait améliorer la prise en charge de ces troubles. Chez l’Homme, des perturbations fonctionnelles du cortex préfrontal médian et du système limbiq...

Declarative memory formation depends on the hippocampus and declines in aging. Two functions of the hippocampus, temporal binding and relational organization (Rawlins and Tsaltas, 1983; Eichenbaum et al., 1992; Cohen et al., 1997), are known to decline in aging (Leal and Yassa, 2015). However, in the literature distinct procedures have been used to...

The behavioral repertoire of an organism can be highly diverse, spanning from social to defensive. How an animal efficiently switches between distinct behaviors is a fundamental question whose inquiry will provide insights into the mechanisms that are necessary for an organism's survival. Previous work aimed at identifying the neural systems respon...

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 durin...

Significance Our ability to form declarative memories depends on the hippocampus, and this capacity degrades with age. To identify the critical determinants of this age-associated memory loss, we explored the relationships between two functions of the hippocampus known to be age-sensitive, temporal binding and relational organization. We found that...

Background: Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala (BLA), an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the BLA involved in this modulation remain to be elucidate...

Accurate predatory behavior requires coordination between pursuit activity and prey consumption, yet the underlying neuronal circuits are unknown. A novel study published in this issue of Cell identifies two coordinated circuits emanating from the central amygdala that control the efficiency of prey capture and the ability to deliver fatal bites to...

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. Wher...

Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey cir...

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 succes...

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 coincid...

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...

How sensory information is transformed by learning into adaptive behaviors is a fundamental question in neuroscience. Studies of auditory fear conditioning have revealed much about the formation and expression of emotional memories and have provided important insights into this question. Classical work focused on the amygdala as a central structure...

Over the past years, numerous studies have provided a clear understanding of the neuronal circuits and mechanisms involved in the formation, expression, and extinction phases of conditioned cued fear memories. Yet, despite a strong clinical interest, a detailed understanding of these memory phases for contextual fear memories is still missing. Besi...

Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral...

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 play a role in cocaine seeking. Howev...

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 condi...

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 (γ-aminobutyric acid)-ergic interneu...

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 spontaneo...

The medial prefrontal cortex 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 onto the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies h...

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 netwo...

Model parameters. Parameters used in the rate and SNN model. (0.13 MB PDF)

ABC renewal and extinction over-training. After fear extinction in context B the activity of extinction neurons (cyan) was high, thereby suppressing the activity of fear neurons (amber) (left). Presenting the CS in the conditioning context-A resulted in a rapid switch of activity, with fear neurons suppressing extinction neurons activity (ABA renew...

Removal of CTX input. (left) Effects of removal of contextual input on fear and extinction neurons activity. When contextual inputs were removed after conditioning, then during extinction simulation no new group of neurons became active and, therefore, fear neurons remained active, as they were the only group of neurons for which CS inputs had been...

Overlapping contextual inputs. (A) Venn diagram illustrating overlap of CTX inputs. (B) Activity of BA neurons at the end of extinction training. Varying the overlap of CTX inputs to BA neurons from 0–100% resulted in a third subgroup, which was active both during conditioning and extinction (persistent neurons). The higher the overlap, the more ne...

The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditione...

Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabil...

The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that ne...

The serine protease inhibitor protease-nexin-1 (PN-1) has been shown to modulate N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic currents and NMDAR-dependent long-term potentiation of synaptic transmission. Here, we analysed the role of PN-1 in the acquisition and extinction of classical auditory fear conditioning, two distinct forms of lea...

Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environme...

Adult Fears Why are fear memories almost impossible to get rid of—even with extensive extinction training? Animal studies have shown that the efficacy of extinction learning depends on age. Fear memories in young animals can be permanently erased, but in adults they can be easily recovered after extinction training. Perineuronal nets, the highly or...

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 glutamatergi...

Switching between exploratory and defensive behaviour is fundamental to survival of many animals, but how this transition is achieved by specific neuronal circuits is not known. Here, using the converse behavioural states of fear extinction and its context-dependent renewal as a model in mice, we show that bi-directional transitions between states...

There is accumulating evidences to suggest that memory consolidation in some conditions involves two waves of neuronal plastic change. Using two fear conditioning procedures in male C57BL/6J mice, we have recently shown that consolidation of the foreground contextual fear memory required two waves of ERK1/2 activation in hippocampal CA1, while cons...

The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in...

One of the fundamental roles of the prefrontal cortex is to inhibit inappropriate responses, as indicated by studies showing that lesions of this structure can result in perseverative behaviors. However, analyses of the involvement of prefrontal neurons in inhibition of conditioned fear responses, during extinction, have led to contradictory observ...

Pavlovian fear conditioning, a simple form of associative learning, is thought to involve the induction of associative, NMDA receptor-dependent long-term potentiation (LTP) in the lateral amygdala. Using a combined genetic and electrophysiological approach, we show here that lack of a specific GABA(B) receptor subtype, GABA(B(1a,2)), unmasks a nona...

Whereas the neuronal substrates underlying the acquisition of auditory fear conditioning have been widely studied, the substrates and mechanisms mediating the acquisition of fear extinction remain largely elusive. Previous reports indicate that consolidation of fear extinction depends on the mitogen-activated protein kinase/extracellular-signal reg...

Fear conditioning is a popular model for investigating physiological and cellular mechanisms of memory formation. In this paradigm, a footshock is either systematically associated to a tone (paired conditioning) or is pseudorandomly distributed (unpaired conditioning). In the former procedure, the tone/shock association is acquired, whereas in the...

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 mor...

Extinction of classical fear conditioning is thought to involve activity-dependent potentiation of synaptic transmission in the medial prefrontal cortex (mPFC), resulting in the inhibition of amygdala-dependent fear responses. While many studies have addressed the mechanisms underlying extinction learning, it is unclear what determines whether exti...

Accumulative evidence indicates that acute (before extinction) and long-lasting (during extinction) depression can occur at excitatory synapses in mouse medial prefrontal cortex (mPFC) during re-exposure to a tone (conditioned stimulus: CS), previously paired with footshock (unconditioned stimulus: US). As recently shown, the long-term depression (...

Considerable efforts have been made to identify changes of brain synaptic plasticity associated with fear conditioning. However, for both clinical applications and our fundamental understanding of memory processes, it appears also necessary to investigate synaptic plasticity related to extinction. We previously showed that extinction of freezing to...

We studied changes in thalamo-prefrontal cortical transmission in behaving mice following both low-frequency stimulation of the mediodorsal thalamus (MD) and during extinction of a conditioned fear response. Electrical stimulation of the MD induces a field potential in the medial prefrontal cortex (mPFC) characterized by two initial negative-positi...