Review
Developmental Biology
Frederic Causeret, Matthieu X. Moreau, Alessandra Pierani, Oriane Blanquie
Summary: Cajal-Retzius neurons (CRs) are among the first-formed neurons in the developing cortex, known for controlling glutamatergic neuron migration and cortical layer formation, as well as playing various additional key roles in cortical development. Recent advancements in single-cell technologies have allowed for a greater understanding of the molecular heterogeneity of CRs and their roles in different species.
Article
Genetics & Heredity
Jia Li, Lei Sun, Xue-Liang Peng, Xiao-Ming Yu, Shao-Jun Qi, Zhi John Lu, Jing-Dong J. Han, Qin Shen
Summary: The study revealed the dynamics of early neuronal differentiation processes through transcriptome and epigenetic analyses, identifying novel coding genes and lncRNAs involved in the differentiation of early neurons. Molecular heterogeneities were found in CR neurons, categorized into three developing states along a pseudotemporal trajectory, showing genetic cascades during the establishment of CR neuron identity and function. The research shed light on the molecular mechanisms governing early differentiation steps in cortical development, specifically CR neuron differentiation.
Article
Multidisciplinary Sciences
Alba Vilchez-Acosta, Yasmina Manso, Adrian Cardenas, Alba Elias-Tersa, Magdalena Martinez-Losa, Marta Pascual, Manuel Alvarez-Dolado, Angus C. Nairn, Victor Borrell, Eduardo Soriano
Summary: The extracellular protein Reelin, derived from both CR cells and GABAergic interneurons, plays a crucial role in regulating the migration and positioning of cortical neurons during development. Disruptions in Reelin can lead to developmental disorders and neuropsychiatric disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Joshua R. Enck, Eric C. Olson
Summary: This study confirms that Cajal-Retzius neurons in the cortical marginal zone can influence the development of cortical projection neurons by releasing glutamate and glycine, providing insight into the observation that many autism-linked genes are expressed in the developing cortex before the appearance of synapses and functional circuits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Matthew J. J. Fogarty
Summary: During development, GABA and glycine play important roles in the neuromotor system, affecting the formation, function and maturation of synapses. This review focuses on GABAergic and glycinergic synapses in neuromotor circuits, discussing the differences in limb and respiratory control. It also explores the effects of GABAergic and glycinergic neurotransmission on two developmental neuromotor disorders, Rett syndrome and spastic cerebral palsy, highlighting the different approaches to disease mechanism and therapy. The article concludes that the diversity of inhibitory neurotransmitter targets offers hope for treating conditions like spastic cerebral palsy and Rett syndrome that exhibit a wide range of dysfunctions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ana Lopez-Mengual, Miriam Segura-Feliu, Raimon Sunyer, Hector Sanz-Fraile, Jorge Otero, Francina Mesquida-Veny, Vanessa Gil, Arnau Hervera, Isidre Ferrer, Jordi Soriano, Xavier Trepat, Ramon Farre, Daniel Navajas, Jose Antonio del Rio
Summary: Evidence suggests that both chemical and mechanical cues play important roles in brain development. Cajal-Retzius cells migrate tangentially in the developing cortex, secreting molecules for correct neocortical layer formation. The motogenic properties and distribution of these cells in the marginal zone are modulated by both chemical and mechanical factors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Neurosciences
Davide Warm, Jonas Schroer, Anne Sinning
Summary: During early brain development, the excitation and inhibition mechanisms play important roles in shaping the neocortex and establishing primary functions. The GABAergic system, as a major inhibitory mechanism, promotes the formation and refinement of neuronal circuits, enabling synchronization within cortical networks and region-specific modulation of neuronal firing.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Nasim Ramezanidoraki, Driss El Ouardi, Margaux Le, Stephanie Moriceau, Mahboubeh Ahmadi, Dossi Elena, Danae Rolland, Philippe Bun, Gwenaelle Le Pen, Guillaume Canaud, Nadia Bahi-Buisson, Nathalie Rouach, Rebecca Piskorowski, Alessandra Pierani, Pierre Billuart
Summary: Cajal-Retzius cells (CRs) are transient neurons in the mammalian cortex that play a critical role in cortical development. Their persistence in postnatal life has been detected in epilepsy-related conditions, but it is unclear if it is a cause or consequence of the diseases. The decrease in PI3K/AKT/mTOR activity in CRs primes these cells to death by possibly repressing a survival pathway, with the mTORC1 branch contributing less to the phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Erwan Leprince, Robin F. Dard, Salome Mortet, Caroline Filippi, Marie Giorgi-Kurz, Romain Bourboulou, Pierre-Pascal Lenck-Santini, Michel A. Picardo, Marco Bocchio, Agnes Baude, Rosa Cossart
Summary: The adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. Neonatal CA1, on the other hand, is tightly linked to externally generated sensorimotor activity, but the circuit mechanisms underlying early synchronous activity in CA1 remain unclear. In this study, researchers use a combination of in vivo and ex vivo circuit mapping, calcium imaging, and electrophysiological recordings in mouse pups to investigate the dynamics in the ventro-intermediate CA1. They find that these dynamics are influenced by both the entorhinal (EC) and thalamic (VMT) inputs, but movement-related population bursts are exclusively driven by the EC. The differential effects reflect the different intrahippocampal targets of these inputs, suggesting distinct contributions to the development of the hippocampal microcircuit and related cognitive maps.
Article
Neurosciences
Sana Al Awabdh, Florian Donneger, Marie Goutierre, Martial Seveno, Oana Vigy, Pauline Weinzettl, Marion Russeau, Imane Moutkine, Sabine Levi, Philippe Marin, Jean Christophe Poncer
Summary: KCC2, a neuron-specific chloride extruder, regulates the strength and polarity of GABAA receptor-mediated transmission and also plays a role in spinogenesis and excitatory synaptic function. The study identifies gephyrin as a novel anchoring molecule for KCC2 that stabilizes its plasma membrane expression and promotes its clustering near GABAergic synapses.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Sharon M. Kolk, Pasko Rakic
Summary: The development of the prefrontal cortex in humans is a complex process, involving the generation, differentiation, and synaptic connection formation of neurons extending into the third decade of life. Neurotransmitter systems and neuronal migration play important roles in this process, with genetic or environmental factors potentially impacting these processes and leading to cognitive impairment.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Jessica L. Sevetson, Brian Theyel, Diane Hoffman-Kim
Summary: This study demonstrates network activity in three-dimensional brain cultures, showing that the networks become more complex over time and can be manipulated with various drugs. The correlations and distances between neurons within the network can be quantified with micron-scale resolution to study emergent network events.
Article
Biochemistry & Molecular Biology
Dipak Roy, Madhuri Puvvada, Sampath K. T. Kapanaiah, Anant Bahadur Patel
Summary: This study used NMR spectroscopy to investigate the metabolic activity of neurons and astrocytes in ALS mice, and found differential changes in metabolic activity, suggesting the involvement of astrocytes in the pathogenesis of ALS.
NEUROCHEMICAL RESEARCH
(2022)
Review
Neurosciences
Tomonori Furukawa, Atsuo Fukuda
Summary: During brain and spinal cord development, the inhibitory neurotransmitters GABA and glycine cause depolarization instead of hyperpolarization in adults. This is influenced by changes in the transmembrane chloride gradient, which is regulated by chloride transporters. The endogenous agonists for these receptors are not fully understood, but taurine is suggested to play a role in the development of neocortex by tonically activating GABA(A)Rs and modulating glycine receptors. Taurine also regulates chloride homeostasis through the WNK-SPAK/OSR1 signaling pathway.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Fanny Lepiemme, Julie Stoufflet, Miriam Javier-Torrent, Gabriel Mazzucchelli, Carla G. Silva, Laurent Nguyen
Summary: During embryogenesis, vOPCs and cortical interneurons interact and occupy mutually exclusive territories in the forebrain. First-wave vOPCs play a crucial role in steering the migration of cortical interneurons away from blood vessels, allowing them to reach their proper cortical territories.
Article
Neurosciences
Svenja L. Kreis, Heiko J. Luhmann, Dumitru Ciolac, Sergiu Groppa, Muthuraman Muthuraman
Summary: This study investigated the connectivity between premotor and primary motor cortex in humans and between caudal and rostral forelimb areas in mice, revealing strong relationships between spectral power, functional connectivity, and effective connectivity.
Review
Neurosciences
Heiko J. Luhmann
Summary: This review article provides a brief summary of the novel technologies, challenges, current understanding, and open questions in the field of neurophysiology of the developing cerebral cortex in rodents. The use of high-density multi-electrode arrays and genetically encoded calcium indicators has allowed the recording of neuronal activity in large cortical networks, revealing surprising patterns of cortical and subcortical activity during early development. However, the functional roles of these activity patterns and their impact on cortical maturation are not yet fully understood. Future research will focus on targeted genetic manipulations and optogenetics to elucidate the function of early cortical circuits and their role in the generation of activity patterns.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Neurosciences
Davide Warm, Jonas Schroer, Anne Sinning
Summary: During early brain development, the excitation and inhibition mechanisms play important roles in shaping the neocortex and establishing primary functions. The GABAergic system, as a major inhibitory mechanism, promotes the formation and refinement of neuronal circuits, enabling synchronization within cortical networks and region-specific modulation of neuronal firing.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Chia-Fang Wang, Jenq-Wei Yang, Zi-Hui Zhuang, Hsiang-Wei Hsing, Heiko J. Luhmann, Shen-Ju Chou
Summary: This study revealed a bottom-up feedback mechanism for regulating the development of TCAs, which involves feedback signals from L4 neurons and the regulation by Lhx2 and Sema7a.
Article
Neurosciences
Jens R. Vandevelde, Jenq-Wei Yang, Steffen Albrecht, Henry Lam, Paul Kaufmann, Heiko J. Luhmann, Maik C. Stuettgen
Summary: Through multi-electrode recordings and behavioral detection, we investigated the importance of different cell types and layers in the brain for the perception of sensory stimuli. Our findings indicate that the highest sensitivity is observed in layer 4, and inhibitory neurons show higher sensitivity compared to excitatory neurons across all layers. Mice perform better when they are not moving, which is reflected by increased firing rates in response to stimuli at the neuronal level.
Article
Neurosciences
Linbi Cai, Jenq-Wei Yang, Chia-Fang Wang, Shen-Ju Chou, Heiko J. Luhmann, Theofanis Karayannis
Summary: The whiskers of rodents play a crucial role in providing tactile information for navigation and object exploration. This study investigates the developmental engagement of different cortical areas in processing whisker stimuli. The researchers find that the primary sensory cortex is activated by sensory stimuli shortly after birth, while the secondary somatosensory area begins to process this information at the end of the first postnatal week. Additionally, the study uncovers a developmental window when information transfer between these cortical areas reaches mature function.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Heiko J. Luhmann, Patrick O. Kanold, Zoltan Molnar, Sampsa Vanhatalo
Summary: This article reviews the methods for assessing neuronal activity in both clinical and animal models, and discusses the urgent need for translational research, the challenges and possible solutions in translating biomedical research into clinical diagnostics or treatments.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Cell Biology
Davide Warm, Davide Bassetti, Jonas Schroer, Heiko J. Luhmann, Anne Sinning
Summary: The early occurrence of calcium transients is strongly linked to neuronal survival, with silent neurons exhibiting a higher probability of cell death. Activity of neighboring neurons in local clusters exerts a pro-survival effect, while networks with a high modular topology are associated with lower cell death rates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Anatomy & Morphology
Levente Gellert, Heiko J. Luhmann, Werner Kilb
Summary: The functional connections between S1 and M1 or S2 are not confined to the same cortical area, but exist already at the day of birth between adjacent cortical areas. These connections play an important role in the development of sensorimotor integration.
FRONTIERS IN NEUROANATOMY
(2023)
Article
Biochemistry & Molecular Biology
Jonas Schroer, Davide Warm, Federico De Rosa, Heiko J. Luhmann, Anne Sinning
Summary: During early brain development, the BAX/BCL-2 pathway plays a role in regulating cortical neuron removal, with electrical activity serving as a set point of regulation. The upregulation of BAX and downregulation of BCL-2 during the first postnatal week result in a high BAX/BCL-2 ratio, contributing to neuronal death rates. Pharmacological blockade of activity leads to upregulation of Bax, while elevated activity leads to increased BCL-2 expression, indicating the modulation of BAX/BCL-2 expression by electrical activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Neurosciences
Heiko J. Luhmann
Summary: This review article provides an overview of the molecular, cellular, and network mechanisms underlying focal seizures in neocortical networks with developmental malformations. Neocortical malformations are a large variety of structural abnormalities associated with epilepsy and other neurological and psychiatric disorders. Animal models and state-of-the-art techniques have contributed to our understanding of neocortical hyperexcitability in developmental disorders. Additionally, molecular biological and electro-physiological techniques have provided insights into the subcellular, cellular, and network mechanisms of focal seizures.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Physiology
Heiko J. Luhmann
Summary: The neocortical network is composed of excitatory and inhibitory neurons, organized in microcircuits that provide various types of neural connections and influences. This network is activated by specific inputs from thalamic nuclei, subcortical regions, and cortico-cortical projections. Different types of neurons in the neocortex have unique firing patterns, synaptic connectivity, and dynamics of their interactions. Repetitive stimulation can activate or inactivate microcircuits within the neocortex. Specific networks within the neocortex generate synchronized activity patterns that contribute to higher cognitive function and behavior. This review provides an overview of the current understanding of the structure and function of the neocortical network.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Psychiatry
Margaryta Tevosian, Hristo Todorov, Ermelinda Lomazzo, Laura Bindila, Natsuo Ueda, Davide Bassetti, Davide Warm, Sergei Kirischuk, Heiko J. Luhmann, Susanne Gerber, Beat Lutz
Summary: AEA is an endogenous ligand of the cannabinoid CB1 and CB2 receptors, playing a protective role against the development of pathological states after prolonged stress exposure. In a study using a genetically modified mouse line, deficiency of the AEA synthesizing enzyme NAPE-PLD in neurons activated during chronic stress led to increased anxiety-like behavior. The molecular mechanisms underlying this phenotype may involve desensitization of the HPA axis, disinhibition of the amygdala by the prefrontal cortex, and altered neuroplasticity in the hippocampus and prefrontal cortex.
TRANSLATIONAL PSYCHIATRY
(2023)
Review
Multidisciplinary Sciences
Daniela Mirzac, Svenja L. Kreis, Heiko J. Luhmann, Gabriel Gonzalez-Escamilla, Sergiu Groppa
Summary: In this article, recent experimental and clinical studies on Parkinson's disease are reviewed, focusing on abnormal neuronal activity and pathological network oscillations and their underlying mechanisms and modulation. The aim is to enhance understanding of the progression of Parkinson's disease pathology and the timing of symptom manifestation. Mechanistic insights on the generation of aberrant oscillatory activity within the cortico-basal ganglia circuits are presented, along with discussions on the advantages, limitations, and differential applicability of available PD animal models, and suggestions for transferring knowledge on disease pathology into future research and clinical applications.
Article
Neurosciences
Aniello Lombardi, Qiang Wang, Maik C. Stuettgen, Thomas Mittmann, Heiko J. Luhmann, Werner Kilb
Summary: This study investigates the role of short-term synaptic plasticity (STP) in excitatory and inhibitory synapses in the cortical layer 2/3 of mice. The results show that burst stimulation leads to short-term depression (STD) in both excitatory and inhibitory synapses, with stronger depression observed in inhibitory synapses and longer decay time.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)