Sevil Duvarci

• PhD
• Group Leader at Goethe University Frankfurt

Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning is not fully understood. Here, in male mice, we demonstrate that DA neurons projecting to a unique subregion of the dorsal striatum, the posterior tail of the striatum (TS), encode a...

Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning is not fully understood. Here, we demonstrate that DA neurons projecting to a unique subregion of the striatum, the posterior tail of the striatum (TS), encode an aversive prediction...

Associative aversive learning enables animals to predict and avoid threats and thus is critical for survival and adaptive behavior. Anxiety disorders are characterized with deficits in normal aversive learning mechanisms and hence understanding the neural circuits underlying aversive learning and memory has high clinical relevance. Recent studies h...

The prefrontal cortex (PFC) is essential for working memory (WM) and has primarily been viewed as being responsible for maintaining information over a delay, but it is unclear whether it also plays a more general role during WM. Using task phase-specific optogenetic silencing of pyramidal neurons in the medial PFC (mPFC) of mice performing a spatia...

The ability to extinguish fear memories when threats are no longer present is critical for adaptive behavior. Fear extinction represents a new learning process that eventually leads to the formation of extinction memories. Understanding the neural basis of fear extinction has considerable clinical significance as deficits in extinction learning are...

Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translat...

It is a joyous relief when an event we dread fails to materialize. In fear extinction, the appetitive nature of an omitted aversive event is not a mere epiphenomenon but drives the reduction of fear responses and the formation of long-term extinction memories. Dopamine emerges as key neurobiological mediator of these related processes.

Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the...

The dopamine (DA) system plays a major role in cognitive functions through its interactions with several brain regions including the prefrontal cortex (PFC). Conversely, disturbances in the DA system contribute to cognitive deficits in psychiatric diseases, yet exactly how they do so remains poorly understood. Here we show, using mice with disease-...

Background: Transient periods with reduced neuronal discharge - called 'pauses' - have recently gained increasing attention. In dopamine neurons, pauses are considered important teaching signals, encoding negative reward prediction errors. Particularly simultaneous pauses are likely to have increased impact on information processing. Comparison w...

The hippocampus and prefrontal cortex have long been known to play a central role in various behavioral and cognitive functions. More recently, electrophysiological and functional imaging studies have begun to examine how interactions between the two structures contribute to behavior during various tasks. At the same time, it has become clear that...

We review recent work on the role of intrinsic amygdala networks in the regulation of classically conditioned defensive behaviors, commonly known as conditioned fear. These new developments highlight how conditioned fear depends on far more complex networks than initially envisioned. Indeed, multiple parallel inhibitory and excitatory circuits are...

This review summarizes the latest developments in our understanding of amygdala networks that support classical fear conditioning, the experimental paradigm most commonly used to study learned fear in the laboratory. These recent advances have considerable translational significance as congruent findings from studies of fear learning in animals and...

The lateral nucleus (LA) is the input station of the amygdala for information about conditioned stimuli (CSs), whereas the medial sector of the central nucleus (CeM) is the output region that contributes most amygdala projections to brainstem fear effectors. However, there are no direct links between LA and CeM. As the main target of LA and with it...

The central amygdala (Ce), particularly its medial sector (CeM), is the main output station of the amygdala for conditioned fear responses. However, there is uncertainty regarding the nature of CeM control over conditioned fear. The present study aimed to clarify this question using unit recordings in rats. Fear conditioning caused most CeM neurons...

Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis...

Brain activity in sleep plays a crucial role in memory consolidation, an offline process that determines the long-term strength of memory traces. Consolidation efficacy differs across individuals, but the brain activity dynamics underlying these differences remain unknown. Here, we studied how interindividual variability in fear memory consolidatio...

While learning to fear stimuli that predict danger promotes survival, the inability to inhibit fear to inappropriate cues leads to a pernicious cycle of avoidance behaviors. Previous studies have revealed large inter-individual variations in fear responding with clinically anxious humans exhibiting a tendency to generalize learned fear to safe stim...

Memory consolidation is the process by which newly learned information is stabilized into long-term memory (LTM). Considerable evidence indicates that retrieval of a consolidated memory returns it to a labile state that requires it to be restabilized. Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in...

A large body of pharmaco-behavioral data implicates the basolateral nucleus of the amygdala (BLA) in the facilitation of memory consolidation by emotions. Overall, this evidence suggests that stress hormones released during emotional arousal increase the activity of BLA neurons. In turn, this increased BLA activity would facilitate synaptic plastic...

Consolidated memories when reactivated may return to a state that requires protein synthesis in order to be restabilized (reconsolidation). It has been shown in a variety of systems that if reactivation induces significant extinction then extinction is the protein synthesis dependent memory state, rather than reconsolidation. Thus, extinction conso...

In recent years, the amygdala has emerged as a critical site of plasticity for the acquisition of various forms of Pavlovian learning, either aversive or appetitive. In most of these models, the critical site of plasticity has been localized to the basolateral complex of the amygdala (BLA). In contrast, the central nucleus of the amygdala has emerg...

Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in the lateral nucleus of amygdala (LA). Recently we have demonstrated that consolidated fear memories, when reactivated, return to a labile state which is sensitive to disruption by the protein synthesis inhibitor anisomycin. The specific molecular mecha...

Reactivation of consolidated memories returns them to a protein synthesis-dependent state. One interpretation of these findings is that the memory reconsolidates after use. Two alternative interpretations are that protein synthesis inhibition facilitates extinction and that postreactivation protein synthesis inhibition leads to an inability to retr...