Combinative Protein Expression of Immediate Early Genes c-Fos, Arc, and Npas4 Along Aversive and Appetitive Experience-Related Neural Networks.

Expression of immediate early genes (IEGs) is critical for memory formation and has been widely used to identify the neural substrate of memory traces, termed memory engram cells. Functions of IEGs have been known to be different depending on their types. However, there is limited knowledge about the extent to which different types of IEGs are selectively or concurrently involved in the formation of memory engram.

Combinative protein expression of immediate early genes c-Fos, Arc, and Npas4 along aversive- and reward-related neural networks.

Expression of immediate early genes (IEGs) is critical for memory formation and has been widely used to identify the neural substrate of memory traces, termed memory engram cells. Functions of IEGs have been known to be different depending on their types. However, there is limited knowledge about the extent to which different types of IEGs are selectively or concurrently involved in the formation of memory engram.

Memory processing by hippocampal adult-born neurons.

This review provides an integrative overview of the functional roles of adult neurogenesis in the hippocampal dentate gyrus (DG), focusing specifically on its impact on memory processes across the lifespan. A distinguishing feature of this review is its systematic approach, organizing the contributions of adult-born neurons (ABNs) chronologically through the stages of memory-from initial encoding, through sleep-dependent consolidation, retrieval, and finally forgetting. Although the existence and extent of adult neurogenesis in the human DG remain debated, accumulating evidence suggests that ABNs support cognitive functions throughout adulthood.

Roles of mediodorsal thalamus in observational fear-related neural activity in mouse anterior cingulate cortex.

Observational fear (OF) is the ability to vicariously experience and learn from another's fearful situation, enabling adaptive responses crucial for survival. It has been shown that the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) are crucial for OF. A subset of neurons in the ACC is activated when observing aversive events in the demonstrator, which elicits OF.

Automated detection of c-Fos-expressing neurons using inhomogeneous background subtraction in fluorescent images.

Although many methods for automated fluorescent-labeled cell detection have been proposed, not all of them assume a highly inhomogeneous background arising from complex biological structures. Here, we propose an automated cell detection algorithm that accounts for and subtracts the inhomogeneous background by avoiding high-intensity pixels in the blur filtering calculation. Cells were detected by intensity thresholding in the background-subtracted image, and the algorithm's performance was tested on NeuN- and c-Fos-stained images in the mouse prefrontal cortex and hippocampal dentate gyrus.

Automated cell detection for immediate early gene-expressing neurons using inhomogeneous background subtraction in fluorescent images.

Unlabelled: Although many methods for automated fluorescent-labeled cell detection have been proposed, not all of them assume a highly inhomogeneous background arising from complex biological structures. Here, we propose an automated cell detection algorithm that accounts for and subtracts the inhomogeneous background by avoiding high-intensity pixels in the blur filtering calculation. Cells were detected by intensity thresholding in the background-subtracted image, and the algorithm's performance was tested on NeuN- and c-Fos-stained images in the mouse prefrontal cortex and hippocampal dentate gyrus.

Understanding Others' Distress Through Past Experiences: The Role of Memory Engram Cells in Observational Fear.

For individuals to survive and function in society, it is essential that they recognize, interact with, and learn from other conspecifics. Observational fear (OF) is the well-conserved empathic ability of individuals to understand the other's aversive situation. While it is widely known that factors such as prior similar aversive experience and social familiarity with the demonstrator facilitate OF, the neural circuit mechanisms that explicitly regulate experience-dependent OF (Exp OF) were unclear.

Diastereomers of Coibamide A Show Altered Sec61 Client Selectivity and Ligand-Dependent Activity against Patient-Derived Glioma Stem-like Cells.

Coibamide A (CbA) is a cyanobacterial lariat depsipeptide that selectively inhibits multiple secreted and integral membrane proteins from entering the endoplasmic reticulum secretory pathway through binding the alpha subunit of the Sec61 translocon. As a complex peptide-based macrocycle with 13 stereogenic centers, CbA is presumed to adopt a conformationally restricted orientation in the ligand-bound state, resulting in potent antitumor and antiangiogenic bioactivity. A stereochemical structure-activity relationship for CbA was previously defined based on cytotoxicity against established cancer cell lines.

Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice.

Entorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons in the EC provide projections to the hippocampus.

Visuotactile integration facilitates mirror-induced self-directed behavior through activation of hippocampal neuronal ensembles in mice.

Remembering the visual features of oneself is critical for self-recognition. However, the neural mechanisms of how the visual self-image is developed remain unknown because of the limited availability of behavioral paradigms in experimental animals. Here, we demonstrate a mirror-induced self-directed behavior (MSB) in mice, resembling visual self-recognition.

Optogenetic activation of dopamine D1 receptors in island cells of medial entorhinal cortex inhibits temporal association learning.

A critical feature of episodic memory formation is to associate temporally segregated events as an episode, called temporal association learning. The medial entorhinal cortical-hippocampal (EC-HPC) networks is essential for temporal association learning. We have previously demonstrated that pyramidal cells in the medial EC (MEC) layer III project to the hippocampal CA1 pyramidal cells and are necessary for trace fear conditioning (TFC), which is an associative learning between tone and aversive shock with the temporal gap.

Design of Synthetic Surrogates for the Macrolactone Linker Motif in Coibamide A.

A marine cyanobacterial cyclic depsipeptide, coibamide A (CbA), inhibits the mammalian protein secretory pathway by blocking the Sec61 translocon, which is an emerging drug target for cancer and other chronic diseases. In our previous structure-activity relationship study of CbA, the macrolactone ester linker was replaced with alkyl/alkenyl surrogates to provide synthetically accessible macrocyclic scaffolds. To optimize the cellular bioactivity profile of CbA analogues, novel lysine mimetics having β- and ε-methyl groups have now been designed and synthesized by a stereoselective route.

Extracting electromyographic signals from multi-channel LFPs using independent component analysis without direct muscular recording.

Electromyography (EMG) has been commonly used for the precise identification of animal behavior. However, it is often not recorded together with electrophysiology due to the need for additional surgeries and setups and the high risk of mechanical wire disconnection. While independent component analysis (ICA) has been used to reduce noise from field potential data, there has been no attempt to proactively use the removed "noise," of which EMG signals are thought to be one of the major sources.

Systems consolidation induces multiple memory engrams for a flexible recall strategy in observational fear memory in male mice.

Observers learn to fear the context in which they witnessed a demonstrator's aversive experience, called observational contextual fear conditioning (CFC). The neural mechanisms governing whether recall of the observational CFC memory occurs from the observer's own or from the demonstrator's point of view remain unclear. Here, we show in male mice that recent observational CFC memory is recalled in the observer's context only, but remote memory is recalled in both observer and demonstrator contexts.

Dissecting cell-type-specific pathways in medial entorhinal cortical-hippocampal network for episodic memory.

Episodic memory, which refers to our ability to encode and recall past events, is essential to our daily lives. Previous research has established that both the entorhinal cortex (EC) and hippocampus (HPC) play a crucial role in the formation and retrieval of episodic memories. However, to understand neural circuit mechanisms behind these processes, it has become necessary to monitor and manipulate the neural activity in a cell-type-specific manner with high temporal precision during memory formation, consolidation, and retrieval in the EC-HPC networks.

Neuronal Ensembles Organize Activity to Generate Contextual Memory.

Contextual learning is a critical component of episodic memory and important for living in any environment. Context can be described as the attributes of a location that are not the location itself. This includes a variety of non-spatial information that can be derived from sensory systems (sounds, smells, lighting, etc.

Poncet's Disease (Reactive Arthritis Associated with Tuberculosis).

An 82-year-old man with miliary tuberculosis was admitted to our hospital. Approximately six weeks after starting anti-tuberculosis treatment, he complained of pain in the fingers, wrists, and ankles. A histopathological examination of the synovial biopsy revealed nonspecific chronic inflammation with no granulomas.

Hippocampal-amygdala memory circuits govern experience-dependent observational fear.

The empathic ability to vicariously experience the other's fearful situation, a process called observational fear (OF), is critical to survive in nature and function in society. OF can be facilitated by both prior similar fear experience in the observer and social familiarity with the demonstrator. However, the neural circuit mechanisms of experience-dependent OF (Exp OF) remain unknown.

Design of Coibamide A Mimetics with Improved Cellular Bioactivity.

Coibamide A, a cyclic depsipeptide isolated from a Panamanian marine cyanobacterium, shows potent cytotoxic activity via the inhibition of the Sec61 translocon. We designed a coibamide A mimetic in which the ester linkage between MeThr and d-MeAla in coibamide A was replaced with an alkyl linker to provide a stable macrocyclic scaffold possessing a MeLys(Me) residue. Taking advantage of a facile solid-phase synthetic approach, an structure-activity relationship (SAR) study of the newly designed macrocyclic structure was performed, with a focus on altering the pattern of -methyl substitution and amino acid configurations.

Synthesis of low-molecular weight fucoidan derivatives and their binding abilities to SARS-CoV-2 spike proteins.

Fucoidan derivatives 10-13, whose basic sugar chains are composed of repeating α(1,4)-linked l-fucopyranosyl residues with different sulfation patterns, were designed and systematically synthesized. A structure-activity relationship (SAR) study examined competitive inhibition by thirteen fucoidan derivatives against heparin binding to the SARS-CoV-2 spike (S) protein. The results showed for the first time that 10 exhibited the highest inhibitory activity of the fucoidan derivatives used.

Learning and memory: Shuffling memory traces by relearning.

Memory engram cells are a subpopulation of neurons activated during learning, and are necessary and sufficient for memory recall. New findings show that relearning induces the turnover of the memory engram cell population involved in fear memory recall.

Hypocrellin B-based activatable photosensitizers for specific photodynamic effects against high HO-expressing cancer cells.

A novel tumor-related biomarker, a HO-activatable photosensitizer 4 based on the 1,3-dicarbonyl enol moieties of hypocrellin B (3), was designed and synthesized. The photosensitizer 4 showed a blue-shifted absorption band compared with 3, and showed negligible photosensitizing ability without HO. However, the release of 3 from 4 by the reaction with HO regenerated the photosensitizing ability.

Entorhinal cortical Island cells regulate temporal association learning with long trace period.

Temporal association learning (TAL) allows for the linkage of distinct, nonsynchronous events across a period of time. This function is driven by neural interactions in the entorhinal cortical-hippocampal network, especially the neural input from the pyramidal cells in layer III of medial entorhinal cortex (MECIII) to hippocampal CA1 is crucial for TAL. Successful TAL depends on the strength of event stimuli and the duration of the temporal gap between events.

Cell-Type-Specific Optogenetic Techniques Reveal Neural Circuits Crucial for Episodic Memories.

The formation and maintenance of episodic memories are important for our daily life. Accumulating evidence from extensive studies with pharmacological, electrophysiological, and molecular biological approaches has shown that both entorhinal cortex (EC) and hippocampus (HPC) are crucial for the formation and recall of episodic memory. However, to further understand the neural mechanisms of episodic memory processes in the EC-HPC network, cell-type-specific manipulation of neural activity with high temporal resolution during memory process has become necessary.