Marie-H Monfils

University of Texas at Austin | UT · Department of Psychology

Fear memories can be updated behaviorally by delivering extinction trials during the reconsolidation window, which results in a persistent attenuation of fear memories (Monfils et al., Science 324:951-955, 2009). This safe and non-invasive paradigm, termed retrieval-extinction (or post-retrieval extinction), has also been found to be successful at...

Introduction Renewal is a behavioral phenomenon wherein extinction learning fails to generalize between different contextual environments, thereby representing a significant challenge to extinction-based rehabilitative therapies. Previously, we have shown that renewal of extinguished appetitive behavior differs across the estrous cycle of the femal...

There is a strong association between traumatic brain injuries (TBIs) and the development of psychiatric disorders, including post-traumatic stress disorder (PTSD). Exposure-based therapy is a first-line intervention for individuals who suffer from PTSD and other anxiety-related disorders; however, up to 50% of individuals with PTSD do not respond...

The ability to acquire information about the environment through social observation or instruction is an essential form of learning in humans and other animals. Here, we assessed the ability of rats to acquire an association between a light stimulus and the presentation of a reward that is either hidden (sucrose solution) or visible (food pellet) v...

Pavlovian conditioning can underly the maladaptive behaviors seen in psychiatric disorders such as anxiety and addiction. In both the lab and the clinic, these responses can be attenuated through extinction learning, but often return with the passage of time, stress, or a change in context. Extinction to fear and reward cues are both subject to the...

Learning can occur via direct experience or through observation of another individual (i.e., social learning). While research focused on understanding the neural mechanisms of direct learning is prevalent, less work has examined the brain circuitry mediating the acquisition and recall of socially acquired information. Here, we aimed to further eluc...

Background Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exp...

Background: Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive-compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of ex...

Activation of the fear system is adaptive, and protects individuals from impending harm; yet, exacerbation of the fear system is at the source of anxiety-related disorders. Here, we briefly review the 'why' and 'how' of fear, with an emphasis on models that encapsulate the elegant complexity of rodents' behavioral responding in the face of impendin...

In this selective review article, we showcase our collaborations with our colleague, Dr. Nadia Chaudhri. Dr. Chaudhri was an esteemed colleague and researcher who contributed greatly to our understanding of Pavlovian alcohol conditioning. From 2014 to 2019, we collaborated with Nadia. Here, we reflect on our friendship, the work we did together, an...

Hormonal contraceptives (HCs) containing synthetic ovarian hormones are commonly used among reproductive aged women; HCs alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As ovarian hormones modulate the incidence of substance abuse disorders in women, this e...

Acquiring fear responses to predictors of aversive outcomes is crucial for survival. At the same time, it is important to be able to modify such associations when they are maladaptive, for instance in treating anxiety and trauma-related disorders. Standard extinction procedures can reduce fear temporarily, but with sufficient delay or with reminder...

The ability to learn new information and behaviors is a vital component of survival in most animal species. This learning can occur via direct experience or through observation of another individual (i.e., social learning). While research focused on understanding the neural mechanisms of direct learning is prevalent, less work has aimed at understa...

[This corrects the article DOI: 10.3389/fnbeh.2013.00164.].

Orexin-producing cells in the lateral hypothalamic area have been shown to be involved in a wide variety of behavioral and cognitive functions, including the recall of appetitive associations and a variety of social behaviors. Here, we investigated the role of orexin in the acquisition and recall of socially transmitted food preferences in the rat....

Acquiring fear responses to predictors of aversive outcomes is crucial for survival. At the same time, it is important to be able to modify such associations when they are maladaptive, for instance in treating anxiety and trauma-related disorders. Standard extinction procedures can reduce fear temporarily, but with sufficient delay or with reminder...

Context is the milieu in which everything occurs. Many research studies consider context, or even explicitly manipulate it; yet it remains challenging to characterize. We know that a context surrounds and influences tasks; however, the boundaries of its influence are difficult to define. In behavioral science, context is often operationalized by th...

Hormonal contraceptives (HCs) are commonly used among reproductive aged women and alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As hormones such as estradiol and progesterone modulate the incidence of substance abuse disorders in women, it is important to...

Renewal of appetitive behavior depends on the gonadal hormonal state of the female rat. In this experiment the effect of female rat estrous cycle stage on renewal of appetitive behaviors is replicated and extended upon to understand how endogenous hormonal states around the estrous cycle drive renewal at the neuronal population level. Estrous cycle...

Conditioned orienting response (OR) is a form of cue-directed behavior thought to indicate increased attentional and/or motivational processing of reward-associated stimuli. OR as a phenotype has been shown to predict both direct drug proclivity in female rats and behaviors indirectly related to drug proclivity in male rats, but no extant research...

Background Pre-extinction fear memory reactivation (PE-FMR) and deepened extinction (DE) enhance long-term extinction of shock-conditioned fear, and may also enhance long-term extinction of naturally acquired fear. Preliminary data suggest that PE-FMR may additionally boost the speed of fear reduction during exposure therapy. Design Randomized con...

Chronic cerebral hypoperfusion in neurocognitive disorders diminishes cytochrome oxidase activity leading to neurodegenerative effects and impairment of learning and memory. Methylene blue at low doses stimulates cytochrome oxidase activity and may thus counteract the adverse effects of cerebral hypoperfusion. However, the effects of methylene blue...

Despite its apparent adaptive advantages, past research has found that greater familiarity and/or familial relatedness of a social demonstrator does not enhance social learning in the social transmission of food preference paradigm. This finding runs counter to research examining the effects of demonstrator characteristics in fear-mediated social l...

In Pavlovian renewal paradigms, intact female rats have previously failed to exhibit renewal of appetitive behavior after extinction. However, when treated with exogenous estradiol, female rats exhibit robust renewal behavior. The current study aims to investigate whether the estrous cycle can influence renewal of appetitive behaviors and activity...

The ability to observe, interpret, and learn behaviors and emotions from conspecifics is crucial for survival, as it bypasses direct experience to avoid potential dangers and maximize rewards and benefits. The anterior cingulate cortex (ACC) and its extended neural connections are emerging as important networks for the detection, encoding, and inte...

The ability of environmental cues to trigger alcohol-seeking behaviors is believed to facilitate problematic alcohol use. We previously showed that the development of this cue-evoked alcohol approach reflects cue-alcohol learning and memory in the adult male rat; however, we do not know whether the same is true for similarly aged female rats. Conse...

Fear conditioning is widely employed to study dysregulations of the fear system. The repeated presentation of a conditioned stimulus in the absence of a reinforcer leads to a decrease in fear responding—a phenomenon known as extinction. From a translational perspective, identifying whether an individual might respond well to extinction prior to int...

Rationale Females are considered more susceptible to the reinforcing effects of drugs and subsequently at increased risk for drug abuse and relapse after treatment. Estrogen is known to facilitate drug effects in females. However, other factors which contribute to the incidence of drug abuse are important to identify in order to recognize early ris...

A more detailed description of the exclusion criteria and excluded participants, and a more exact characterization of the final dataset are provided in the Supplementary Information to the accompanying Addendum.

Pioneering research over the past two decades has shown that memories are far more malleable than we once thought, thereby highlighting the potential for new clinical avenues for treatment of psychopathology. We first briefly review the historical foundation of memory reconsolidation-a concept that refers to hypothetical processes that occur when a...

Direct exposure to stimuli in their environment is not the only way that animals learn about important information. Individuals can infer fear from a social context through observation. Like humans, rats are very social animals, and may learn to infer information about their environment through their interactions with conspecifics. Here, we first r...

In the social transmission of food preference paradigm, naive observer rats acquire safety information about novel food sources in the environment through social interaction with a demonstrator rat that has recently eaten said food. Research into the behavioural mechanisms governing this form of learning has found that observers show increased reli...

We describe a method of social fear transmission to a discrete auditory cue in freely behaving rats. Extending beyond traditional observer/demonstrator paradigms, rats are allowed to physically interact and integrate cues from all sensory modalities. In the protocol described in this article, “observer” rats experience social fear conditioning thro...

Pairing a neutral cue (e.g., a tone) with an inherently aversive unconditioned stimulus (US; e.g., a footshock) creates an associative memory such that later presentations of the now conditioned stimulus alone elicit a conditioned fear response (e.g., freezing). This direct associative learning is only one technique through which individuals can le...

We examined the enduring effects of predictable versus unpredictable fear conditioning early in life on memory and relearning in adulthood. At postnatal Day 17 or 25 (P17 or P25), rats either remained naïve, or were fear conditioned using paired (predictable) or unpaired (unpredictable) presentations of white noise and foot shocks. At 2 months of a...

Fear conditioning is widely employed to examine the mechanisms that underlie dysregulations of the fear system. Various manipulations are often used following fear acquisition to attenuate fear memories. In rodent studies, freezing is often the main output measure to quantify ‘fear’. Here, we developed data-driven criteria for defining a standard b...

Implicit learning about antecedent stimuli and the unconditional stimulus (US) properties of alcohol may facilitate the progressive loss of control over drinking. To model this learning, Cofresí et al. (2017) developed a procedure in which a discrete, visual conditional stimulus (houselight illumination; CS) predicted the availability of a retracta...

Background: Exposure therapy, a behavioral approach to reduce symptomology in fear, anxiety, and drug-related psychiatric disorders, is based on learning and memory principles of extinction, and is subject to relapse. As such, it is important to find ways to enhance outcomes. One such way is through exercise. Objectives: Identify if exercise aug...

Recently, alternative drug therapies for Parkinson’s disease (PD) have been investigated as there are many shortcomings of traditional dopamine-based therapies including difficulties in treating cognitive and attentional dysfunction. A promising therapeutic avenue is to target mitochondrial dysfunction and oxidative stress in PD. One option might b...

Background: Exposure therapy is an established learning-based intervention for the treatment of anxiety disorders with an average response rate of nearly 50%, leaving room for improvement. Emerging strategies to enhance exposure therapy in humans and fear extinction retention in animal models are primarily pharmacological. These approaches are lim...

Many factors account for how well individuals extinguish conditioned fears, such as genetic variability, learning capacity and conditions under which extinction training is administered. We predicted that memory-based interventions would be more effective to reduce the reinstatement of fear in subjects genetically predisposed to display more extinc...

We tested postretrieval extinction as an augmentation strategy for enhancing in vivo exposure therapy for naturally acquired pathological fear. Participants displaying marked phobic responding to either spiders or snakes were randomized to receive a standard one session in vivo exposure therapy protocol under one of two conditions. The experimental...

Background: Conditioned responses to alcohol-associated cues can hinder recovery from alcohol use disorder (AUD). Cue exposure (extinction) therapy (CET) can reduce reactivity to alcohol cues, but its efficacy is limited by phenomena such as spontaneous recovery and reinstatement that can cause a return of conditioned responding after extinction....

Fear extinction typically results in the formation of a new inhibitory memory that suppresses the original conditioned response. Evidence also suggests that extinction training during a retrieval-induced labile period results in integration of the extinction memory into the original fear memory, rendering the fear memory less susceptible to reinsta...

Empathy is a phenomenon often considered dependent on higher-order emotional control and an ability to relate to the emotional state of others. It is, by many, attributed only to species having well-developed cortical circuits capable of performing such complex tasks. However, over the years, a wealth of data has been accumulated showing that roden...

Acquiring information about stimuli that predict danger, through either direct experience or inference from a social context, is crucial for individuals’ ability to generate appropriate behaviors in response to threats. Utilizing a modified demonstrator–observer paradigm (fear conditioning by proxy) that allows for free interaction between subjects...

Traumatic experiences early in life can contribute to the development of mood and anxiety disorders that manifest during adolescence and young adulthood. In young rats exposed to acute fear or stress, alterations in neural development can lead to enduring behavioral abnormalities. Here, we used a modified extinction intervention (retrieval+extincti...

Retrieving a memory can modify its influence on subsequent behavior. Whether this phenomenon arises from modification of the contents of the memory trace or its accessibility is a matter of considerable debate. We develop a computational theory that incorporates both mechanisms. Modification of the contents of the memory trace occurs through classi...

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed r...

Pavlovian fear conditioning is one of the most common and well-understood methods for studying fear learning. However, research is predominantly performed in males. Recently, in a classical Pavlovian fear conditioning paradigm, Gruene and colleagues described an active conditioned fear response ('darting') prevalent in female rats that better maint...

While the definition of the limbic system has evolved since Paul Broca first described the distinct set of cortical structures on the medial surface of the cerebrum, the major structures have remained fairly consistent. Here we describe the major anatomical structures most commonly included in the limbic system and explore their major behavioral an...

Fear conditioning (FC) is a model that has been extremely well characterized over the years, and which has proven invaluable in improving our understanding of the neural basis of anxiety-related disorders. The neural mechanisms that contribute to anxiety per se are less easily isolated into components; yet, owing to significant overlap between the...

Freezing has become the predominant measure used in rodent studies of conditioned fear, but conditioned suppression of reward-seeking behavior may provide a measure that is more relevant to human anxiety disorders; that is, a measure of how fear interferes with the enjoyment of pleasurable activities. Previous work has found that an isolated presen...

Over the past century, numerous theories have been advanced toward a unified account of fear reduction and have achieved various degrees of empirical support. Here, we first provide a brief overview of the basic models that account for fear acquisition, then we provide a review of several of the most prominent theories of fear reduction, and finall...

Brain-derived neurotrophic factor (BDNF) is associated with synaptic plasticity, which is crucial for long-term learning and memory. Some studies suggest that people suffering from anxiety disorders show reduced BDNF relative to healthy controls. Lower BDNF is associated with impaired learning, cognitive deficits, and poor exposure-based treatment...

Retrieval of consolidated memories induces a labile phase during which memory can be disrupted or updated through a reconsolidation process. A central component of behavioural updating during reconsolidation using a retrieval-extinction manipulation (Ret + Ext) is the synaptic removal of a calcium-permeable–α-amino-3-hydroxyl-5-methyl-4-isoxazole-p...

Chronic cerebral hypoperfusion, a risk factor for mild cognitive impairment and Alzheimer's disease, affects mitochondrial respiration and memory consolidation. Therefore, drugs that improve mitochondrial function may be appropriate cognitive treatments for cerebral hypoperfusion. Methylene blue (MB) crosses the blood-brain barrier and at low doses...

Our objective was to characterize individual differences in fear conditioning and extinction in an outbred rat strain, to test behavioral predictors of these individual differences, and to assess their heritability. We fear-conditioned 100 Long-Evans rats, attempted to extinguish fear the next day, and tested extinction recall on the third day. The...

Animal models of fear conditioning provide insight into ways to reduce the intensity of a fear memory and attenuate its associated response. Two popular methods to reduce fear in animals are extinction, in which the animal is repeatedly exposed to the fear-inducing stimulus in the absence of any negative outcome, and reconsolidation blockade/update...

When presented with a light cue followed by food, some rats simply approach the foodcup (Nonorienters), while others first orient to the light in addition to displaying the food-cup approach behavior (Orienters). Cue-directed orienting may reflect enhanced attentional and/or emotional processing of the cue, suggesting divergent natures of cue-infor...

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing). Individuals can also acquire fear from a social context, such as through observing the fear expression of a co...

INDIVIDUAL DIFFERENCES IN APPETITIVE LEARNING HAVE LONG BEEN REPORTED, AND GENERALLY DIVIDE INTO TWO CLASSES OF RESPONSES: cue- vs. reward-directed. The influence of cue- vs. reward-directed phenotypes on aversive cue processing, is less well understood. In the current study, we first categorized rats based on their predominant cue-directed orienti...

Significance An advantage of targeting reconsolidation to control reactions to learned threats is that the memory appears to be persistently altered, not inhibited. When these memories are diminished through extinction, the amygdala’s representation remains largely intact and the prefrontal cortex inhibits its expression, thus allowing the learned...

Fear memories are notoriously difficult to erase, often recovering over time. The longstanding explanation for this finding is that, in extinction training, a new memory is formed that competes with the old one for expression but does not otherwise modify it. This explanation is at odds with traditional models of learning such as Rescorla-Wagner an...

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window attenuate...