Fear memory

…prelimbic cortex (PL) is required for fear memory retrieval across time and is densely interconnected with many subcortical and cortical areas involved in recent and remote memory recall, including the temporal association area (TeA). While the behavioral expression of a memory may remain constant over time, the neural activity mediating memory-guided behavior is dynamic. In PL, different neurons underlie recent and remote memory retrieval and remote memory-encoding neurons have

Astrocytes are active players in brain function. They sense and respond to neuronal activity by elevating intracellular calcium levels. These calcium elevations exhibit complex spatiotemporal patterns across the soma and main processes and focal microdomains. This activity underlies the astrocytic involvement in synaptic transmission, metabolism, and brain homeostasis. Here, we performed a multi-level analysis of the IP3 receptor type 2 knockout (IP3R2 KO) mouse model lacking global calcium elevations in astrocytes to disclose its implications to the molecular, cellular, and behavior levels. T

Understanding the neural circuitry involved in fear memory is expected to provide implications for mental disorders such as post-traumatic stress disorder. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) are essential for the consolidation of fear memories. This consolidation occurs in particular when BLA neurons responding to aversive stimuli are reactivated during non-REM sleep. However, the neural circuit mechanism during non-REM sleep remains unclear. We focus on the role of neocortical slow waves, a hallmark of non-REM sleep, in fear memory formation. By recording l

…error (PE) signal during associative fear learning. These DA neurons are necessary specifically during acquisition of fear learning, but not once the fear memory is formed, and are not required for forming cue-reward associations. Notably, tem

Background: This study explores how threat learning contributes to the development of fear and anxiety. We aim to determine if observed responses indicate a general novelty marker, are solely linked to arousal, and are influenced by valence. Adopting the transdiagnostic RDoC approach, this study focuses on acute and sustained threat within negative valence systems.Aims: Utilizing a modified Threat Conditioning and Extinction Task (TCET), we examined fear memory traces in healthy over three phases (preconditioning, conditioning, extinction). The study involved subjective ratings of faces associ

Several anxiety-related neuropsychiatric disorders are associated with amygdala dysfunction during early periods of postnatal development, and adolescence is a particularly vulnerable emotional period. Among the cellular mechanisms involved in changes in the activity of individual neurons and their synaptic connections, the mTOR signaling pathway has been proposed as a molecular regulator of emotional memories and could thus constitute a common mechanistic source of the emergence of anxiety symptoms in these disorders. We hypothesize that amygdala mTOR dysfunction during infancy can initiate a

Research in humans has long recognized a modulating role for sex hormones on fear learning. There is still not quite a consensus on what specific effects different hormones have, or what experimental paradigm properly reflects key processes of fear-related learning in near-ecological situations. Our aim with this work was to precisely tackle the influence of sex hormones and the menstrual cycle in fear memory, combining for the first time methods such as vaginal cytology analysis, liquid chromatography-mass spectrometry (LC-MS), fear-potentiated startle (FPS) and skin conductance response (SCR

Fear-related memory traces are encoded by sparse populations of hippocampal principal neurons that are recruited based on their inhibitory–excitatory balance during memory formation. Later, the re-activation of the same principal neurons can recall the memory. The details of this mechanism are still unclear. Here, we investigated whether disinhibition could play a major role in this process. Using optogenetic behavioral experiments we found that when fear was associated with the inhibition of mouse hippocampal somatostatin positive interneurons, the re-inhibition of the same interneurons could

The habenula is a phylogenetically conserved bilateral brain structure known to modulate negative emotions. Hemispheric asymmetry in cortical areas plays a key role in behavior and cognition. Although habenular asymmetry is prominent in several vertebrate species, there is little evidence for left-right asymmetry in the mammalian habenula. To investigate the asymmetry in synaptic transmission in the medial habenula (MHb) to the interpeduncular nucleus (IPN) pathway in mice, we performed targeted electrical stimulation of left or right MHb-derived axons in acute slices. We discovered that the p

Early life stress (ELS) due to neglect or abuse, has profound and lasting effects on adult neural function, contributing to various psychopathologies. Utilizing the well-established model of early life maternal separation (ELMS), this study investigated the impact of ELS on adult behavior. For the maternally separated (MS+) group, pups were separated from their mother for 3 hours from postnatal day 1 to 14, while control (stress naive) group pups remained in their home cages. Behavioral assessments from week 8-10 (young adults) revealed significant differences between MS+ and control mice. Bot

Light-Sheet Fluorescence Microscopy (LSFM) is an excellent tool to study neuronal populations in large samples such as the whole mouse brain, thanks to its inherent three-dimensional nature and its high resolution down to the single cell. In this work we report on our latest technological developments in both hardware and software and their applications in several projects aiming at reconstructing the neuronal organization in both the human cortex and in whole mouse brain.Our latest LSFM setup is capable of simultaneous excitation and acquisition at four wavelengths, thus enabling fast reconst

Neuropeptide Y (NPY) is the most abundant neuropeptide in the brain, co-expressed with other neurotransmitters. It is expressed mainly by interneurons in different regions, including the hippocampus (HP). NPY binds to five G-protein-coupled receptors (R), from which Y1 and Y2 R are the most numerous in the rodent brain. NPY is implicated in the regulation of stress and can exert anxiolytic or anxiogenic effects, depending on the specific brain region and receptor subtype being activated. HP and specifically its ventral portion, contributes to this processing with an important role in emotional

…mice lacking IP3R2 display enhanced fear memory. Molecular analysis of hippocampal tissues revealed hundreds of up or down-regulated genes, among which 76 of those are m

…bodily feedback signals to alleviate fear, shedding light on new forms of non-invasive interventions. First, learning proactive coping actions to avoid threats leads to persistent fear-alleviating effects relative to passive extinction procedures (Cain and LeDoux 2007), suggesting that bodily actions could facilitate resilience to learned threats. Second, physiological bodily responses under threat, such as changes in respiration and heart rate, serve as feedback signals to regulate fear (Karalis & Sirota, Nat Comm, 2022; Hsueh e

Fear responses are functionally adaptive behaviors that are strengthened as memories. Indeed, detailed knowledge of the neural circuitry modulating fear memory could be the turning point for the comprehension of this emotion and its pathological states. A comprehensive understanding of the circuits mediating memory encoding, consolidation, and retrieval presents the fundamental technological challenge of analyzing activity in the entire brain with single-neuron resolution. In this context, we develop the brain-wide neuron quantification toolkit (BRANT) for mapping whole-brain neuronal activati

Cancer survivors treated with chemotherapy experience persistent memory deficits, commonly known as ‘chemofog’. Currently there are no effective treatments for chemotherapy-induced cognitive impairment, and the underlying molecular mechanisms are poorly understood. Recent evidence suggests that chemotherapy induces chronic microglia reactivity, the brain’s resident immune cells, which could drive alterations in neuroplasticity mechanisms ultimately causing memory impairment. In this study we want to investigate the role of microglia in chemotherapy-induced learning and memory impairment in a r