Review
Biochemistry & Molecular Biology
Gabriel Berdugo-Vega, Shonali Dhingra, Federico Calegari
Summary: This article reviews a wealth of research in cellular, anatomical, behavioral, and computational studies on the mammalian hippocampus, aiming to understand the fundamental mechanisms underlying cognition. Despite accumulating knowledge on how the hippocampus processes and stores information for learning and memory, our understanding of hippocampal cognitive function remains incomplete. The article discusses the structural separability of the two blades of the dentate gyrus in the hippocampus and proposes a model that suggests differences in connectivity and adult neurogenesis in the two blades may contribute to subtly different cognitive functions.
Review
Neurosciences
Jesse D. Cushman, Michael R. Drew, Franklin B. Krasne
Summary: The primary function of juvenile and adult hippocampal neurogenesis appears to be allowing behavioral experience to shape connectivity in the dentate gyrus and optimize hippocampal circuits for future learning. This environmental sculpting reduces overlap among memory representations, provides more information, and allows for more memories to be stored accurately. The decline of neurogenesis prior to adulthood may be explained by this prospective function of sculpting hippocampal circuits.
PROGRESS IN NEUROBIOLOGY
(2021)
Review
Cell Biology
Luka Culig, Xixia Chu, Vilhelm A. Bohr
Summary: Adult neurogenesis is a potential target for extending cognitive healthspan, as aging is a major risk factor for neurodegenerative diseases. This review describes the role of adult neurogenesis in neurodegenerative diseases and discusses the molecular mechanisms involving key proteins. Interventions that increase neurogenesis and regulate aging research targets are summarized, and the outlook for restoring neurogenesis levels in elderly individuals and those with neurodegeneration is shared.
AGEING RESEARCH REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Timothy J. Schoenfeld, Chance Swanson
Summary: Physical exercise has wide-ranging benefits to cognitive functioning and mental state, with effects resembling enhancements to hippocampal functioning. Beta-endorphins released during exercise are a potential candidate for moderating increases in neurogenesis and related behavioral benefits. Further exploration of beta-endorphin as a key mediator of hippocampal neurogenesis could provide insights into how exercise promotes adult neurogenesis and overall brain health.
Article
Neurosciences
Nanami Kasakura, Yuka Murata, Asuka Shindo, Shiho Kitaoka, Tomoyuki Furuyashiki, Kanzo Suzuki, Eri Segi-Nishida
Summary: The dentate gyrus of the hippocampus plays a regulatory role in stress-related emotional behaviors and neurogenesis. NT-3 is expressed in the adult dentate gyrus and is enhanced under chronic stress conditions in rodents. However, the functional modulation of the dentate gyrus by NT-3 signaling is still unclear.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Kyle R. Jensen, Coralie Berthoux, Kaoutsar Nasrallah, Pablo E. Castillo
Summary: Recurrent excitatory neural networks in the hippocampus involving excitatory mossy cells (MCs) can promote epilepsy. Physiologically relevant activity patterns of MCs induce robust presynaptic long-term potentiation (LTP) of MC-GC transmission. Type-1 cannabinoid receptors (CB1Rs) at MC axon terminals play a crucial role in modulating presynaptic metaplasticity and excitatory transmission onto granule cells (GCs).
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Chuanqi Liu, Jiayin Liu, Hong Gong, Tianyao Liu, Xin Li, Xiaotang Fan
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by atypical social communication and repetitive sensory-motor behaviors. Emerging evidence suggests that deficits in hippocampal neurogenesis may play a significant role in the abnormal behaviors observed in ASD. This review summarizes pre-clinical and clinical studies supporting the importance of hippocampal neurogenesis in the pathogenesis of ASD, discusses the potential of enhancing hippocampal neurogenesis as a new therapeutic strategy for ASD, and highlights the prospects of pro-neurogenic therapies for ASD.
CURRENT NEUROPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Viktor Aniol, Anna Manolova, Natalia Gulyaeva
Summary: The dentate gyrus (DG), an important part of the hippocampus, is affected by early life stress, which can cause long-lasting changes in its structure and functioning. This review comprehensively discusses the effects of early life events on the maturation of neurons and glial cells in the DG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Eri Tabuchi, Takeshi Sakaba, Yuki Hashimotodani
Summary: Recent evidence suggests that glutamate and GABA can be coreleased from the same presynaptic terminals in certain adult brain regions, such as the SuM-DG pathway. The LTP of glutamatergic transmission selectively increases excitatory drive, contributing to network activity in the DG region.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Geriatrics & Gerontology
Heather Bondi, Valeria Bortolotto, Pier Luigi Canonico, Mariagrazia Grilli
Summary: This study found that astrocytes in the hippocampus and entorhinal cortex of middle-aged mice have different responses to aging. Astrocytes in the dorsal DG showed a significant increase in morphological complexity, while astrocytes in the ventral DG and entorhinal cortex underwent remarkable changes. These findings suggest a new level of complexity in structural changes associated with brain aging.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Renee C. Waters, Hunter M. Worth, Betsy Vasquez, Elizabeth Gould
Summary: Early life adversity increases the risk of developing neuropsychiatric illnesses, and adult neurogenesis may play a role in buffering against the detrimental stress-induced outcomes. This study suggests that there may be sex differences in the role of adult-born neurons in regulating behavior changes induced by early life adversity.
NEUROBIOLOGY OF STRESS
(2022)
Article
Neurosciences
Shawn F. Sorrells, Mercedes F. Paredes, Zhuangzhi Zhang, Gugene Kang, Oier Pastor-Alonso, Sean Biagiotti, Chloe E. Page, Kadellyn Sandoval, Anthony Knox, Andrew Connolly, Eric J. Huang, Jose Manuel Garcia-Verdugo, Michael C. Oldham, Zhengang Yang, Arturo Alvarez-Buylla
Summary: Adult hippocampal neurogenesis was initially discovered in rodents, with subsequent studies identifying adult neural stem cells and their links to plasticity, behavior, and disease. The debate continues as to whether new neurons are produced in the human dentate gyrus during healthy aging. Recent research has shown conflicting results regarding the presence of dividing neuronal precursors in the adult human brain.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Virendra Tiwari, Akanksha Mishra, Sonu Singh, Shubha Shukla
Summary: Neural stem cells (NSCs) are the functional and developmental unit of neurogenesis, and they have the ability to self-renew and generate new neurons in different neurogenic niches. Neurogenesis in adult brain is associated with synaptic plasticity, learning, and memory, particularly in the dentate gyrus (DG) of the hippocampus and olfactory bulb. Impaired neurogenesis has been implicated as a culprit in age-associated neurological disorders, including Alzheimer's disease (AD). This review provides evidence for the association between impaired neurogenesis and AD, and discusses the molecular and cellular regulation of neurogenesis in the young and aging brain. The review also summarizes therapeutic strategies for targeting the manipulation of the neural stem cell pool and factors affecting this pool in AD.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Cell & Tissue Engineering
Sebastian B. Arredondo, Daniela Valenzuela-Bezanilla, Sebastian H. Santibanez, Lorena Varela-Nallar
Summary: The subgranular zone of the hippocampal dentate gyrus is a neurogenic niche that contains neural stem cells capable of generating granule neurons. Wnt ligands play diverse roles in regulating adult hippocampal neurogenesis. Understanding the cellular source and mechanisms of Wnt signaling will be crucial for future therapeutic interventions.
Review
Neurosciences
Kylie A. Huckleberry, Rebecca M. Shansky
Summary: Neurogenesis in the dentate gyrus contributes to the formation of a heterogeneous DG with specialized adult-born neurons. More research is needed to consider the unique functions of adult-born neurons and to address critical gaps in current studies.
Article
Cell & Tissue Engineering
Ricarda Stock, Pauline Jeckel, Udo Kraushaar, Richard Wuest, Andreas Fallgatter, Hansjuergen Volkmer
Summary: Patient-derived iPSCs are a valuable tool for studying unique disease mechanisms and potential preclinical drug development. Transcriptomic analyses and functional read-outs are the most promising approaches for uncovering specific disease mechanisms in vitro.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Review
Neurosciences
Rinki Saha, Martin Kriebel, Rachel Anunu, Hansjuergen Volkmer, Gal Richter-Levin
Summary: The amygdala plays a crucial role in emotional memory formation and memory modulation in other brain regions. Emotional experiences can induce changes in the amygdala that modify its activity and plasticity, leading to alterations in how an animal responds to subsequent challenges. The amygdala also interacts with other emotion processing regions, resulting in intra-amygdala and trans-regional metaplasticity, which can impact behavior.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Anne Albrecht, Elhanan Ben-Yishay, Gal Richter-Levin
Summary: Behavioral profiling is introduced as a translational approach to distinguish trauma-affected animals from resilient ones, utilizing multiple behavioral tests. Enhanced local inhibition in specific circuits of the dorsal dentate gyrus may be associated with observed symptoms.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2021)
Article
Psychiatry
Marion Bonneau, Shane T. O' Sullivan, Miguel A. Gonzalez-Lozano, Paul Baxter, Phillippe Gautier, Elena Marchisella, Neil R. Hardingham, Robert A. Chesters, Helen Torrance, David M. Howard, Maurits A. Jansen, Melanie McMillan, Yasmin Singh, Michel Didier, Frank Koopmans, Colin A. Semple, Andrew M. McIntosh, Hansjurgen Volkmer, Maarten Loos, Kevin Fox, Giles E. Hardingham, Anthony C. Vernon, David J. Porteous, August B. Smit, David J. Price, J. Kirsty Millar
Summary: The balanced t(1;11) translocation disrupting DISC1 is associated with schizophrenia and affective disorders. Studies on a mutant mouse model, Der1, revealed dysregulation in synaptic function and plasticity, impacting neurotransmission. Furthermore, alterations in pyramidal neurons and interneurons suggest vulnerability to common schizophrenia-associated genetic variants.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Neurosciences
Pauline Jeckel, Martin Kriebel, Hansjuergen Volkmer
Summary: The passage explains the connection between autism spectrum disorder and excitatory/inhibitory imbalance in neuronal network connectivity. It discusses how gene mutations, including Met and downstream components, impact synapse formation and stabilization, and highlights Met's role in stabilizing GABAergic synapses through gephyrin clustering.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Radha Raghuraman, Anoop Manakkadan, Gal Richter-Levin, Sreedharan Sajikumar
Summary: Exposure to juvenile stress has long-term effects on the plasticity and quality of associative memory in adulthood. The high expression of the epigenetic marker G9a/GLP complex is found to be one of the mechanisms underlying this effect. Blocking the G9a/GLP complex can alleviate the deficits in long-term plasticity and associative memory caused by juvenile stress.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Kuldeep Tripathi, Yunus Emre Demiray, Stefanie Kliche, Liang Jing, Somoday Hazra, Joyeeta Dutta Hazra, Gal Richter-Levin, Oliver Stork
Summary: Regional, temporal and molecular specificity in the regulation of GABAergic signaling in stress-responsive circuitry complicates the use of systemic GABAergic modulators for stress-related psychopathology treatment. Reduction of GAD65 expression in the dorsal dentate gyrus has been shown to provide resilience to juvenile stress-induced emotional and cognitive deficits.
NEUROBIOLOGY OF STRESS
(2021)
Review
Health Care Sciences & Services
Thalia Richter, Barak Fishbain, Gal Richter-Levin, Hadas Okon-Singer
Summary: The current psychiatric diagnostic procedure relies heavily on self-reports, which can be biased, highlighting the need for data-driven tools to improve accuracy. While some studies have shown promising results in depression diagnosis using machine learning analysis, most patients do not have access to neuroimaging tools, emphasizing the necessity for objective assessment tools that can be easily integrated into routine diagnostic processes.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Psychiatry
Maayan Krispil-Alon, Vladimir Jovasevic, Jelena Rudulovic, Gal Richter-Levin
Summary: Contrary to intuition, most individuals are resilient to psychological trauma and only a minority is vulnerable. The mechanisms underlying the relationship between sex differences and trauma resilience and vulnerability are not yet fully understood. This study reveals a critical sex-associated difference in the role of miRNAs in stress vulnerability and resilience.
TRANSLATIONAL PSYCHIATRY
(2022)
Correction
Psychiatry
Maayan Krispil-Alon, Vladimir Jovasevic, Jelena Radulovic, Gal Richter-Levin
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Somoday Hazra, Joyeeta Dutta Hazra, Rani Amit Bar-On, Yanhong Duan, Shahaf Edut, Xiaohua Cao, Gal Richter-Levin
Summary: Traumatic stress exposure can lead to persistent trauma-related memories. In this study, a rat model of PTSD was used to differentiate between individuals affected and unaffected by trauma. Inhibiting CaMKII or reducing alpha CaMKII expression in the hippocampus resulted in a decrease in the number of affected individuals. Additionally, reducing alpha CaMKII expression facilitated the formation of alpha CaMKII-independent LTP, potentially enhancing resilience in the face of trauma.
NEUROBIOLOGY OF STRESS
(2022)
Article
Genetics & Heredity
Gil Ben David, Yam Amir, Kuldeep Tripathi, Lital Sharvit, Amir Benhos, Rachel Anunu, Gal Richter-Levin, Gil Atzmon
Summary: Epigenetics is a gene-environment interaction mechanism that manifests through changes in gene expression. Stress is a known environmental factor that can induce epigenetic changes. This study investigated the impact of stress during adolescence or both adolescence and adulthood on glutamic acid decarboxylase genes. The findings suggest that juvenile stress may enhance coping strategies, but additional stress in adulthood can elicit contradictory responses, which may be beneficial or harmful.
Review
Cell Biology
Gil Ben David, Yam Amir, Randa Salalha, Lital Sharvit, Gal Richter-Levin, Gil Atzmon
Summary: Psychiatric disorders have a significant impact on individuals and their families, with substantial costs to society. Personalized medicine offers a solution, but finding genetic biomarkers for treatment efficacy has been challenging. This review emphasizes the potential of epigenetics as a tool for predicting treatment efficacy and personalizing medicine for psychiatric disorders. While still in its early stages, epigenetics shows promise in examining individual patients' epigenetic profiles alongside other indicators. Further research, including additional studies and validation, is needed for its application.
Article
Clinical Neurology
Liang Jing, Chen Ma, Lin Xu, Gal Richter-Levin
Summary: A single exposure to a significant emotional challenge can lead to the development of either an active or reactive coping style in otherwise healthy individuals, with distinct neural correlates and subsequent behavioral significance. Active avoidance (AA) is associated with beneficial outcomes, such as reduced behavioral despair and improved spatial learning, while reactive escape (RE) leads to impaired spatial retrieval.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2023)
